Summary metastatic disease to the spine the the most common location for metastases to bone 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), osteoprotegrin 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 hyper-reflexia Evaluation Workup for older patient with single bone lesion and unknown primary includes imaging AP and lateral of spine in region of pain 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 survery labs CBC with differential ESR basic metabolic panel LFTs, Ca, Phos, alkaline phosphatase serum and urine immunoelectrophoresis (SPEP, UPEP) 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 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 CT scan helpful to identify metastatic lesions to the spine MRI useful to show neurologic compromise of the spine Studies Histology characteristic findings epithelial cells in clumps or glands in a fibrous stroma immunohistochemical stains positive Keratin CK7 (breast and lung cancer) TTF1 (lung cancer) 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 palliative care indications life expectancy of < 6 months Tokuhashi scoring system can be used to determine life expectancy radiation alone indications may be indicated in patients who are not surgical candidate no signs of neural compression, neurologic deficit, or instability Operative neurologic decompression, spinal stabilization, and postoperative radiation indications metastatic lesions to spine with neurologic deficits in patients with life expectancy of > 6 months technique preoperative embolization indicated in metastatic renal and thyroid CA to spine Complications Recurrence Hardware failure and spinal instability Nonunion of fracture Wound complications 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 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)