Summary Metastatic disease to the spine the the most common location for metastases to bone that can lead to significant morbidity. This condition typically occurs in older cancer patients and presents with axial night pain and/or neurologic deficits. Diagnosis is typically made with MRI with contrast which shows a soft tissue mass with possible cord compression or vertebral fractures Treatment depends on the structural damage and symptoms caused by the lesion as well as patient prognosis (NOMS framework). Stable fractures in patients not able to undergo major surgery can be treated nonoperative or with minimally invasive techniques. Large lesions in patients with a good prognosis can be treated with laminectomy, fusion, and possibly corpectomy. Radiation therapy can be used as an adjunctive therapy Introduction Metastatic cancer is the most common reason for a destructive bone lesion in adults carcinomas that commonly spread to bone include breast (16-37% of breast cancer patients develop spine mets) lung (12-15%) thyroid (4%) renal (3-6%) prostate (9-15%) Epidemiology Incidence bone is the 3rd most common site for metastatic disease (behind lung and liver) up to 90% of patients with metastatic cancer have spinal disease, but only 10-20% are symptomatic Demographics metastatic bone lesions are usually found in older patients (> 40 yrs) Anatomic location common sites of metastatic lesions include spine>proximal femur>humerus most common site of mets is spine thoracic spine is most common site of bony metastasis 2nd most common site of mets is proximal femur proximal femur is most common site of fracture secondary to metastatic bone lesions 65% nonunion rate 50% in femoral neck, 20% pertrochanteric, 30% subtrochanteric Etiology Pathophysiology mechanism of bone destruction (osteolysis) osteolytic bone lesions are caused by tumor-induced activation of osteoclasts occurs through the RANK, RANK ligand (RANKL), osteoprotegerin pathway PTHrP positive breast cancer cells activate osteoblastic RANKL production osteoblastic bone metastases are due to tumor-secreted endothelin 1 Associated conditions metastatic hypercalcemia occurs in 10-30% of patients most common in lung and breast cancer a medical emergency symptoms include confusion muscle weakness polyuria & polydipsia nausea/vomiting dehydration treatment hydration (volume expansion) loop diuretics bisphosphonates anemia common thromboembolic disease increased risk due to hypercoagulable state Principles of metastasis Mechanism of metastasis two hypotheses seed and soil: tumor cells grow in compatible end-organ environments circulation theory: tumor spread is primarily influenced by blood flow from the primary site tumor cell intravasation E cadherin cell adhesion molecule (on tumor cells) modulates release from primary tumor focus into bloodstream avoidance of immune surveillance target tissue localization attaches to target organ endothelial layer via integrin cell adhesion molecule (expressed on tumor cells) extravasation into the target tissue induction of angiogenesis via vascular endothelial growth factor (VEGF) expression genomic instability decreased apoptosis Vascular spread Batson's vertebral plexus valveless venous plexus of the spine that provides a route of metastasis from organs to axial structure including vertebral bodies, pelvis, skull, and proximal limb girdles Mechanism of bone lysis oncogenic cell releases cytokines TNF-alpha, IL-6, IL-11, PTHrP, TGF-beta PTHrP and TGF-beta activate osteoblasts osteoblasts secrete RANKL, that binds to RANK on osteoclasts and activates osteoclasts Mechanism of bone sclerosis (prostate and breast mets) prostate cancer cells secrete endothelin 1 (ET-1) ET-1 binds to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts ET-1 decreasesWNT suppressor DKK-1 activates WNT pathway, increasing osteoblast activity breast cancers can produce sclerosis which represses osteoblasts Classification Tokuhashi score specific to metastatic disease to spine prognostic score based on 6 elements: general condition, extraspinal bony metastasis, number of vertebral bodies with metastasis, visceral metastasis, primary tumor, neurologic compromise score of 0-8: <6 months; 9-12 > 6 months, 12-15 >1 year Symptoms History unexplained rest pain or mechanical back/neck pain in cancer patients constitutional symptoms (weight loss, fatigue, malaise) risk factors of common cancers (smoking, hematuria, shortness of breath, breast mass, goiter) current and prior chemotherapy treatment can cause peripheral neuropathy Symptoms pain axial night pain may be mechanical pain due to bone destruction or tumorigenic pain which often occurs at night metastatic hypercalcemia Physical exam neurologic deficits caused by compression of the spinal cord with metastatic disease to the spine important to differentiate between root level and cord level injury gait abnormalities hyperreflexia Evaluation Workup for older patients with single bone lesion and unknown primary includes imaging AP and lateral of spine in region of pain MRI with contrast including limited sagittal views of the rest of the spine CT of chest / abdomen / pelvis technetium bone scan to detect extent of disease myeloma and thyroid carcinoma are often cold on bone scan - evaluate with a skeletal survey labs CBC with differential ESR basic metabolic panel LFTs, Ca, Phos, alkaline phosphatase serum and urine immunoelectrophoresis (SPEP, UPEP) thyroid function test parathyroid hormone PSA urinalysis biopsy in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion should not treat a bone lesion without tissue diagnosis of the lesion metastatic adenocarcinoma not identified by CT of the chest, abdomen, and pelvis is most likely from a small lung primary tumor technique posterior-based transpedicular approach increased risk of vertebral artery injury with posterior approach wide-gauge Jamshidi cannula coring needle imaging guidance (fluoroscopy, CT, or navigation) See table of evaluation algorithms based on patient factors Imaging Radiographic recommended views AP and lateral of involved area off spine findings purely lytic or mixed lytic/blastic lesions lung, thyroid, and renal are primarily lytic 60% of breast CA is blastic 90% of prostate CA is blastic up to 40% of lesion will not be visible on radiographs CT scan helpful to identify metastatic lesions to the spine sensitivity 66% and specificity 99% CT myelography is best imaging study for patients who have a contraindication to MRI CT chest/abdomen/pelvis is needed for the work up of an unknown primary tumor MRI with contrast dedicated MRI of the area of interest with limited sagittal views of the rest of the spine useful to show neurologic compromise of the spine findings soft tissue mass increased signal on T2 images cortical permeation cord compression 98% sensitive and specific Studies Histology characteristic findings epithelial cells in clumps or glands in a fibrous stroma immunohistochemical stains positive (depending on primary cancer) Keratin CK7 (breast and lung cancer) TTF1 (lung cancer) Vimentin (renal) CDX2 (colon) Treatment General considerations NOMS framework: neurologic, oncologic, mechanical instability, systemic illness neurologic: measure of epidural spinal cord compression (ESCC) 0-1 low grade, 2-3 high grade oncologic: responsiveness to radiation mechanical instability: spinal instability neoplastic score (SINS) SINS: 0-6 no surgical consultation required, 7-18 surgical consultation advisable systemic illness: formulation of prognosis from disease burden, medical comorbidities, functional status Nonoperative pain management and bracing indications stable fractures no neurologic deficits life expectancy of < 6 months Tokuhashi scoring system can be used to determine life expectancy Operative kyphoplasty/vertebroplasty, ablation, and radiation indications no fracture or stable fracture no signs of neural compression, neurologic deficit, or instability outcomes 88% chance of local control after stereotactic radiosurgery in tumors not causing instability or cord compression neurologic decompression, spinal stabilization, and postoperative radiation indications metastatic lesions to spine with neurologic deficits in patients with life expectancy of > 6 months intractable pain technique preoperative embolization indicated in metastatic renal and thyroid CA to spine outcomes 95% local control after surgery and radiation 16% of ASIA E patients with high grade epidural cord compression have neurologic decline even with surgery Technique kyphoplasty/vertebroplasty, ablation, and radiation performed under fluoroscopic guidance percutaneous transpedicular approach used for cannula radiofrequency ablation thermal ablation results in destruction of tumor cells can be followed by kyphoplasty/vertebroplasty kyphoplasty cavity created with expansion device (e.g., balloon) prior to PMMA injection may be possible to obtain partial reduction of fracture with balloon expansion neurologic decompression, spinal stabilization, and postoperative radiation approach typically posterior for thoracic, lumbar, and sacral spine costotransversectomy allows for resection of the posterior elements, disc, and corpectomy from a single approach anterior or posterior for the cervical spine depending on lesion, deformity, and number of affected levels large vertebral lesions leading to deformity may require corpectomy laminectomies can be performed for decompression cement used to increase screw pullout goal is removal of all disease, but often the margin will be intralesional Complications Recurrence Hardware failure and spinal instability increased risk due to radiation, chemotherapy, and host frailty Nonunion of fracture Wound complications and infection Immediate soft tissue reconstruction has a lower complication rate than delayed reconstruction in patients undergoing revision metastatic spine tumor surgery Prognosis mean time for cancer patients to develop a spine metastasis is 32 months mean time from spinal metastasis to fracture is 27 months 1 year survival for patients who undergo surgery for spine metastases is 50% epidural disease worsens the prognosis Factors that influence survival histology and prior treatment functional status and neurologic function age extent of metastatic disease nutritional status Median survival in patients with metastatic bone disease thyroid: 48 months prostate: 40 months breast: 24 months kidney: variable depending on medical condition but may be as short as 6 months lung: 6 months Tokuhashi score (see classification section)