SPINE SBRT: The MSKCC Spine Service IAEA Singapore SBRT Symposium Josh Yamada MD FRCPC Mark Bilsky MD Departments of Radiation Oncology and Neurosurgery Memorial Sloan Kettering Cancer Center NY NY USA Disclosures Varian Medical Systems Consultant Continuing Medical Education Institute Speakers Bureau MSKCC Spine Service Radiation Oncology Josh Yamada, M.D. Radiology Eric Lis, M.D. George Krol, M.D. Sasan Karimi, M.D. Pierre Gobin, M.D. Athos Patsilides, M.D. Orthopedic Surgery Patrick Boland, M.D. Neurosurgery Mark Bilsky, M.D. Ilya Laufer, M.D. Neurology Edward Avila, D.O. Xi Chen, M.D. Sonia Sandhu, D.O Physiatry Michael Stubblefield,M.D. Jonas Sokolof, D.O. Christian Custodio, M.D. PT/OT Nursing Joan Zatcky, NP Cynthia Correa, RN Pain Ruth Gargan-Klinger, NP Jane Yoffe, NP Roma Tickoo, M.D. Solange Inglis, NP Kenneth Cubert, M.D. Marie Marte, NP Vinay Puttaniah, M.D. Amitabh Gulati, M.D. Goals of Treatment Multi-disciplinary Approach • Metastasis • Palliation Pain Control Neurology Oncology Mechanical 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 Considerations NOMS1,2 • Neurologic • Systemic Therapy • Oncologic • Radiation Therapy • Mechanical Stability • Surgery • Systemic disease vs. 1Bilsky MH, Smith M. Surgical approach to epidural spinal cord compression. Hematology/Oncology Clinics of North America.;20(6):1307-1317, 2006 2Bilsky 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 Therapy Multi-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/rotation SAC: Flexion/extension Thoracic: Extension Lumbar: 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) Neuropathy Brachial/Lumbosacral Plexus Tumor Leptomeningeal Tumor • Treatment: Dependent on tumor histology and degree of ESCC, often RT in absence of instability Presentation • Myelopathy: • Indicative of high-grade ESCC Spinothalamic tracts (Pinprick) Corticospinal tracts (Motor) Posterior Columns (Proprioception) Autonomic (Bowel and Bladder) Neurogenic vs. other (eg. narcotics) Perineal numbness Conus medullaris or sacrum Other 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 0 ESCC N: 1 O: Radiation Sensitivity Radiation Tumor Sensitivity Histology Sensitive 2 3 Myeloma Lymphoma Moderately Sensitive Breast Moderately Resistant Colon NSCLC Highly Resistant Thyroid Renal Sarcoma Melanoma NOMS 0 N: ESCC O: Radiation Sensitivity 1 Radiation Tumor Sensitivity Histology Sensitive 2 3 cEBRT 30 Gy in 3 Gy/fraction Myeloma Lymphoma Moderately Sensitive Breast Moderately Resistant Colon NSCLC Highly Resistant Thyroid Renal Sarcoma Melanoma NOMS 0 N: ESCC 1 O: Radiation Sensitivity Radiation Tumor Sensitivity Histology Sensitive 2 3 SRS Myeloma Lymphoma Moderately Sensitive Breast Moderately Resistant Colon NSCLC Highly Resistant Thyroid Renal Sarcoma Melanoma NOMS 0 N: ESCC O: Radiation Sensitivity 1 Radiation Tumor Sensitivity Histology Sensitive 2 3 Surgery + SRS Myeloma Lymphoma Moderately Sensitive Breast Moderately Resistant Colon NSCLC Highly Resistant Thyroid Renal Sarcoma Melanoma Histologic Classification Radiosensitivity to cEBRT (30 Gy in 10) Lymphoma Seminoma Myeloma Breast Prostate Sarcoma Melanoma GI NSCL C Renal Gilbert F F U U U U U U Maranzano F F F U U U U U Rades F I I I U I U I Rades F F F U U U U U Katagiri F F F U U U U U Maranzano F F F U U U U U Rades F I I I U I U I Responses: F-Favorable, I-Intermediate, U-Unfavorable 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 Local Control Histology 413 patients Histology 3 Yr Local Control Breast 98% GI 98% H&N 93% Lung 98% Melanoma 90% Unknown 91% Prostate 98% Renal 89% Sarcoma 96% Thyroid 92% 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 Case Solitary T10 RCC RCC/Melanoma Stereotactic 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 paradigm For 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 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 SR S RCC SRS:24 Gy, Cord dMax:14Gy f/u 26 months Bilsky M,, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009. RCC 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. SRS:24 Gy, Cord dMax:14Gy f/u 26 months Bilsky M,, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009. NOMS 0 N: ESCC O: Radiation Sensitivity 1 Radiation Tumor Sensitivity Histology Sensitive 2 3 Surgery + SRS Myeloma Lymphoma Moderately Sensitive Breast Moderately Resistant Colon NSCLC Highly Resistant Thyroid Renal Sarcoma Melanoma 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 cord Subtherapeutic dose that spares spinal cord tolerance risks epidural tumor progression • Resolution of soft tissue disease can take months: Under-dosed sub-volume No effective decompression of epidural disease • Caveat: SRS for RT-sensitive disease (Median 16Gy)1 Cord Tumor (gross Tumor (gross target volume) target volume) 1Ryu S., et.al Radiosurgical decompression of metastatic epidural compression. Cancer 116(9): 2250, 2010 Prescription isodose 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 surgery 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 Results Overall Ambulation Duration Surgery Radiation Significance 84% (42/50) 57% (29/51) p=.001 13 days p=.003 19% (3/16) p= .012 122 days Recover Ambulation 62% (10/16) 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 Results Overall Ambulation Duration Surgery Radiation Significance 84% (42/50) 57% (29/51) p=.001 13 days p=.003 19% (3/16) p= .012 122 days Recover Ambulation 62% (10/16) 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 •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 Klekamp J, Samii. Surgical results for spinal metastases. Resection Acta Neurochir (Wien) 140 (9):957-967, 1998 Postoperative Adjuvant Radiation •MSKCC Data: 21 patients • RT-resistant tumors: 100% Melanoma Renal Cell Carcinoma Sarcoma Colorectal 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 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 Local Control Surgery + SRS LD:40% HD:94% 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 Local Control Separation Surgery + SRS 192 pts. SRS: 90% Hypo LD:78% Hypo HD: 95.8% “Separation Surgery” + SRS 86 year old Papillary thyroid ASIA C Absent proprioception N: HG ESCC O: RT-resistant M: Stable S: Tolerable “Separation Surgery” + SRS RCC En bloc excision • Published literature: • 6 case series:15 patients •Operative times: 8 to 12 hours •Transfusion data: Melcher - PRBC-15.7units/FFP20units •No complications reported Bilsky M, et.al. Shifting Paradigms in the Treatment of Metastatic Spine Disease .Spine. 34(22S) Supplement:S101-S107, 2009. •Recurrences:13% 2 “Separation Surgery” + SRS • 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 NOMS Assessment • Neurologic • Myelopathy • Functional Radiculopathy • Degree of epidural spinal cord compression • Oncologic • Tumor Histology: RCC • Radiation or Chemosensitivity • Mechanical Stability NOMS Assessment • Neurologic • Myelopathy • Functional Radiculopathy • Degree of epidural spinal cord compression • Oncologic • Tumor Histology: RCC • Radiation or Chemosensitivity • Mechanical Stability 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 steroids Embolization 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 steroids cEBRT (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 steroids Establish 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 Spine Instability Neoplastic Score (SINS) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral 3 1 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) 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) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral None 3 1 0 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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) SINS Component Description Score Location Junctional (Occ-C2, C7-T2, T11-L1, L5S1) Mobile (C3-6, L2-4) Semirigid (T3-10) Rigid (S2-5) 3 2 1 0 Yes* Occasional non-mechanical pain No 3 1 0 Bone Lesion Lytic Mixed Blastic 2 1 0 Alignment Subluxation / translation De novo deformity Normal 4 2 0 Vertebral Body >50% collapse <50% collapse No collapse with >50% VB involved None of above 3 2 1 0 Posterolateral Involvement Bilateral Unilateral 3 1 Pain Tallied Score from 6 components Stable 0-6 Potentiall Unstable y Unstable 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 SRS NOMS Algorithm 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