Magnetic Resonance Imaging Today magnetic resonance imaging (MRI) provides the most complete informa- tion for evaluating a vertebral metastatic lesion and therefore it has become the imaging modality of choice [6]. MRI is both sensitive and specific and is recom- mended as the initial study in patients with suspected metastatic spinal disease. It clearly provides: tumor localization (unifocal vs multifocal) extent of bony destruction (sometimes better seen on CT) soft tissue involvement localization of neural compression (anterior, posterior, foraminal) MRI is the imaging study of choice The application of contrast medium is helpful when intrathecal metastasis is sus- pected. Repeat MRI studies can demonstrate evolution of the disease process with minimum discomfort to the patient. Characteristic MRI findings ( Fig. 3a, b) suggestive for spinal metastasis are: bone marrow replacement with decreased signal on T1- and increased signal on T2-weighted images preservation of disc structure on both T1- and T2-weighted images spinal cord compression on T1-weighted images compression of subarachnoid space on T2-weighted images contrast enhancement of the metastatic vertebral body ab Figure 3. MRI characteristics of spinal metastases The predominant findings of spinal metastases are the bone marrow replacement with decreased signal intensity on a T1W and increased signal on b T2W images, the preservation of disc structure on both T1W and T2W images, the spinal cord compression on T1W images and the compression of subarachnoid space on T2W images. 982 Section Tumors and Inflammation CT Scans The CT scan is superior only in the assessment of cortical bone and it has nowa- days been surpassed by MRI [6]. It can be of value when extensive spinal recon- structions are required to improve preoperative planning. Bone Scans A bone scan should be performed as screening for extraspinal tumor involvement A radionucleotide bone scan of the skeleton is routinely performed as a screening to rule out the presence of metastatic disease in the spine and other areas of the skeleton. Bone scanning is very sensitive and may predate radio- graphic changes of osteolytic or osteoblastic disease by 2–18 months [22]. It is not specific to metastatic lesions and will be positive in a variety of benign processes [30]. However, false negative findings can occur with very aggres- sive rapidly growing metastatic lesions and multiple myeloma [17]. Success- fully treated metastases are inactive and may also produce normal bone scans [17]. Angiography Because of the lack of specificity and the occurrence of negative scans, this imag- ing modality has distinct limitations in evaluating the presence of metastatic dis- ease. It provides poor visualization of the bony structures and cannot evaluate the presence of spinal canal compromise. For a conclusive screening of the spine, bone scanning has been surpassed by MRI. Angiography is helpful to embolize major feeder vessels in highly vascularized metastasis Angiography has demonstrated to be also very helpful in evaluating the extent of the tumor, the localization of major feeder vessels, and in providing a vehicle for embolization as primary treatment or in association with surgical resection, e.g. highly vascularized renal tumors. Biopsy A biopsy is a must prior to treatment Either open or percutaneous vertebral biopsy can be performed and it is indi- cated to confirm metastatic disease in a patient with a known primary tumor, to evaluate a suspicious radiographic lesion, or to provide tissue for hormonal eval- uation. Always consider a second primary tumor It is important to consider that the metastasis is not necessarily due to the known primary tumor but may be a result of a new so far unknown second pri- mary tumor. Percutaneous biopsy is better performed using a large biopsy needle in order to obtain a sufficient amount of tissue. An anterolateral approach is occasionally used in the cervical spine while a posterior transpedicular approach is preferred in the thoracic and lumbar spine. The biopsy can be performed under image CT guidance is preferred for optimal biopsy intensifier control but CT guidance is preferable because of the more accurate spatial resolution. The accuracy rate for percutaneous bone biopsies is reported to be 95% in diagnosing metastatic lesions and the complication rate is as low as 0.2% [26, 27]. Laboratory Investigation Routine blood studies are non-specific and often not very helpful in diagnosing spinal metastases. However, for a comprehensive tumor screening the following investigations are recommended: Spinal Metastasis Chapter 34 983 complete blood count calcium phosphorus alkaline phosphatase urea creatinine total proteins tumor markers Hypercalcemia frequently occurs in cancer patients Hypercalcemia, which is frequently observed in cancer patients with metastatic disease, is thought to be the result of either resorption of bone in osteolytic lesions or tumor secretion of bone resorbing humoral substances. Tumors often produce antigens or markers that can be recognized with modern radioimmuno- assays. The most frequently used antigens are the carcinoembryonic antigen (CEA) and the prostatic specific antigen (PSA). Classification Numerous classifications have been proposed to describe the clinical presenta- tion (pain, neurologic function, radiographic changes) and results of treatment for patients with spinal metastases. As the treatment of malignant diseases advances and the percentage of patients developing symptomatic metastases increases, there has been a clear need for a better selection of patients requiring thesetreatments.Themostrecentscoring systems [12, 19, 20, 23, 33–36] not only take into account the: local extension of the spinal lesion but are also based on: general health status of the patients neurologic conditions primary site of the cancer number of spinal metastases existence of extraspinal bone metastases involvement of major internal organ metastases Classification systems help to guide further management According to these classification systems, it ispossible to formulate guidelines for the treatment corresponding to patient condition and estimated length of sur- vival. The most recently introduced Tokuhashi scoring system is based on six parameters to assess the severity of the metastatic spinal disease [33, 34]: general condition of the patient (Karnofsky performance status) [23] number of extraspinal metastases number of vertebral metastases metastases to major organs primary tumor site (length of survival) severity of spinal cord palsy (Faenkel’s grades) Each of the six parameters is graded from 2 (positive) to 0 points (negative per- spective). Their score allows the prediction of a postoperative survival period (<3 months with 5 points or less, >12 months with 9 or more points) and there- fore the indication for surgical management for each patient with spinal metasta- sis. 984 Section Tumors and Inflammation Non-operative Treatment The treatment of symptomatic spinal metastases remains controversial. The can- cer patient should not be withheld modern advances in medical care, even if they are merely palliative. The general goals of treatment are ( Table 1): Table 1. General goals of treatment relieve pain reverse or prevent a neurologic deficit restore spinal stability correct spinal deformity cure the disease (in case of a solitary metastasis) improve remaining quality of life It is important to maintain realistic treatment goals, which are to provide pain relief and to prevent the complications of the metastatic disease process, espe- cially neurologic complications. Symptomatic spinal metastases can be treated with various treatment options including: hormonal treatment chemotherapy steroids radiation therapy surgical interventions However, for most cases a combination of these options is best suited. The choice of therapy is also based on the general objectives of treatment. A multidisciplinary approach is mandatory Ideally every patient should benefit from a multidisciplinary team approach involving oncologists, radiotherapists and spinal surgeons, in order to find the best management concept and timing. Steroids Steroids are used initially in acute neurologic deterioration In acute neurologic deterioration, the use of steroids has been shown to be effec- tive in stabilizing and sometimes reversing neurologic dysfunction. Dexametha- sone has been demonstrated to reduce the spinal cord edema and pain associated with some spinal column tumors. Dosage schemes range from a low dose of dexamethasone (16 mg/day in divided doses) to very high doses (96 mg/day) [7]. The optimal dose which is necessary to treat patients with acute spinal cord com- pression is somewhat controversial. In addition, it is unclear whether high doses areassociatedwithimprovedneurologicoutcomeswhencomparedtolow-to- Higher dose steroid treatment is not proven to be better than low-dose treatment moderate doses. High-dose steroids are associated with significantly higher complication rates such as hyperglycemia, gastrointestinal ulceration and perfo- ration, and avascular necrosis of the hip. In addition, steroids may affect the yield of biopsy specimens of undiagnosed spinal masses. Radiotherapy Radiation therapy has become a well-established modality for the treatment of symptomatic skeletal metastases. Significant pain relief has been reported to occur in 70–90% of patients, probably depending on the etiology of the tumor [3]. When evaluating patients with possible neoplastic cord compression for radiotherapy, it is important todetermine the tumor sizeand extent, pathological grade, relative radiosensitivity and whether the source of compression is from Spinal Metastasis Chapter 34 985 the tumor mass or whether it is from bony fragments. Favorable indications for radiotherapy are ( Table 2): Table 2. Indications for radiation therapy radiosensitive tumor neurologic deficit is either stable or slowly progressing spinal canal compromise resulting from soft tissue impingement multiple myelographic blocks no evidence of spinal instability systemic condition of the patient precludes surgical consideration widespread spinal metastatic disease poor prognosis for long-term survival Radiation therapy is rou- tinely used in symptomatic skeletal sensitive metastases Patients with significant neoplastic bony destruction willoftenhaveconcomitant pathological vertebral fractures, with retropulsion of vertebral body fragments into the spinal canal that may impinge on the spinal cord. Radiotherapy has no chance of relieving the compression in these cases. In addition, the bony destruc- tion may result in destabilization of the spinal column, which may predispose the patient to future neurologic injury. These patients are best managed with surgi- cal decompression and stabilization in case their overall medical condition will permit surgery. The standard radiotherapy protocol for palliation of spinal tumors is 300 cGy daily fractions up to a total dose of 3000 cGy. A single posterior field or opposed fields are used to encompass the involved segments plus one to two levels above and below [7]. The tolerance of the spinal cord and cauda equina to radiation therapy is the major limiting factor in treatment with higher doses of radiation. Higher doses increase the risk of developing radiation-induced myelopathy with resultant loss of spinal cord function. After the decision to proceed with radiotherapy has been made, the timing must be carefully considered. Several studies have shown that radiotherapy has deleterious affects on wound and bone healing as well as bone graft incorpora- tion. The negative affects of radiation on skin healing have also been well docu- mented. The operative incision must be taken into account when developing a radiation treatment plan to prevent potentially disastrous wound dehiscence and infection. However, delayed postoperative therapy (>21 days) has not been showntohavethissamenegativeaffectandradiotherapyispresentlyusedin combination with surgery in the majority of spinal metastases operated on [3, 10, 16, 38]. Delayed postoperative radiotherapy is the preferred treatment Operative Treatment General Principles Before recommending a surgical intervention, several factors should be consid- ered. The surgeon must determine whether the patient is an appropriate surgical candidate. This consideration should include [3]: life expectancy of the patient (at least 3–6 months) immunologic status nutritional status tissue conditions (previous radiotherapy) pulmonary function should be evaluated and taken into consideration A formal tumor staging is required prior to treatment In this context, a formal tumor staging is required and classification of the spinal metastasis (e.g. Tokuhashi score) is often helpful. 986 Section Tumors and Inflammation The general indications for surgery are (Table 3): Table 3. General indications for surgery intractable pain progressive neurologic compromise spinal instability and deformity potentially curable disease radioresistant tumors failure of radiotherapy failure of chemotherapy need for open biopsy General Surgical Techniques Percutaneous Vertebroplasty Vertebroplasty is better performed if the posterior vertebral wall is intact Vertebroplasty was first developed for the treatment of vertebral angiomas and the indications have been successively extended to osteoporotic vertebral frac- tures and spinal metastases [14]. The procedure is generally performed using local anesthesia with fluoroscopic or CT guidance. From a posterior approach, thevertebroplastyneedle(about8–10gauge)isintroducedthroughatranspedi- cular approach to the center of the vertebral body. Polymethylmethacrylate or special vertebroplasty cements are injected under careful radiological control. The goal of the procedure is pain relief (obtained in >80% of cases) and the con- solidation of the vertebra avoiding further collapse. Vertebroplasty is performed in the thoracic and lumbar spine. Pathological fractures with an intact posterior wall are the best indication. In experienced hands, the technique can be per- formed under very careful fluoroscopy control also in cases with some degree of posterior wall destruction. Decompressive Laminectomy Laminectomy alone is rarely indicated Decompressive laminectomy alone is rarely indicated because metastatic lesions normally arise from the vertebral body and result in epidural compression that is either anterior or anterolateral to the thecal sac. In these cases, laminectomy is not effective. It produces spinal instability and is reported not to be more effec- tive than radiotherapy in the improvement of neurologic deficits [21, 37]. However, posterior decompression without instrumentation is indicated in: tumors arising from the posterior elements and producing posterior epidu- ral compression patients with multiple vertebral involvements without spinal instability rapidly progressive paralysis in very advanced tumor stage (where extensive spinal procedures would be ill advised) Prophylactic laminectomy sometimes over several levels can be indicated but should better be done in conjunction with spinal instrumentation to avoid fur- ther vertebral collapse. Metastatic tumors involving the upper cervical spine (C1 or C2) are difficult to address with an anterior approach. Due to the wide spinal canal in this particular area of the spine, they can be treated with decompressive laminectomy, realign- ment of the spine and posterior segmental instrumentation extended to the occi- put ( Case Study 1) [25]. Spinal Metastasis Chapter 34 987 Tumor Resection and Spinal Stabilization In contrast to decompressive laminectomy, the general goals of treatment ( Table 1) in metastatic spinal tumors are best accomplished by: decompression of neural structures debulking (or, if possible, en bloc resection) of the metastasis realignment of spinal deformity spinal reconstruction/stabilization However, the feasibility of the various approaches depends on: location and extent of neural impingement number of vertebrae involved region of the spine affected need for spinal stabilization patient’s medical condition Specific Surgical Techniques Cervical Spine Tumors involving a vertebral body between C3 and C7 (possibly T1) can be easily approached with classical anterolateral exposure of the cervical spine [25]. For this surgery, the patient is placed prone on the operating table with the cervical spine in extension and mild skull traction. Patient intubation may need to be per- formed under endoscopic guidance due to the severe spinal instability. Following exposure of the spine, the affected vertebral body and the two adjacent discs are Corpectomy and anterior column reconstruction is the therapy of choice for vertebral body lesions completely resected to the posterior longitudinal ligament. Care is taken always to work in a posterior-to-anterior direction and never towards the spinal canal. The realignment of the cervical spine is easy and mainly occurs spontaneously after the vertebrectomy is completed. The reconstruction of the vertebral body is obtained using bone cement or a special reconstruction cage and spinal fixation with anterior plate and screws is finally performed to produce a solid spinal sta- bilization ( Case Introduction). In the cervical spine, a two or more level involve- ment will require additional posterior instrumentation. Tumors involving C1/C2, multilevel cervical metastases, or the cervicothora- cic junction without spinal instability are better addressed from posterior as pre- viously described [25, 29]. One or multilevel level laminectomy combined with a plate/rod fixation using lateral mass screws or possibly pedicle screws will pro- vide spinal stabilization ( Fig. 4). Metastases at the craniocer- vical and cervicothoracic junctions are better treated from posterior (if possible) Metastatic tumors involving the upper cervical spine (C1 or C2) are difficult to address with an anterior approach. Due to the wide spinal canal in this particular area of the spine, they can be treated with decompressive laminectomy,realign- ment of the spine and posterior segmental instrumentation extended to the occiput ( Case Study 1). Thoracic Spine Tumors involving the thoracic spine between T7 and T12 can be easily approached through a standard thoracotomy [3, 7, 8, 18, 35]. The segmental ves- sels, which course in the vertebral body depressions between the intervertebral Solitary thoracic vertebral body metastases are best treated by anterior corpectomy and spinal reconstruction discs, are ligated and divided. The intervertebral discs are completely resected back to the posterior longitudinal ligament. The tumoral mass is progressively removed down to the posterior longitudinal ligaments with rongeurs, curettes and, if necessary, high-speed drills. Following an adequate corpectomy,thepos- 988 Section Tumors and Inflammation a bc d Figure 4. Treatment of metastasis at the cervicothoracic junction a, b A 41-year-old lady with a history of breast cancer and multilevel vertebral metastases and cord compression in the cervicothoracic junction. c, d Decompressive laminectomies and multilevel posterior stabilization with lateral mass screws in C4 and C5, and pedicle screws from C7 to T6, were performed at surgery. a b cd e fg Case Study 1 A 74-year-old man with a history of lung adenocarcinoma presented with disabling upper neck pain resistant to major pain medication. Physical examination revealed adequate general health and a normal neurologic status. Radiological assessment including plain X-rays and MRI showed a pathological fracture of C2 with severe instability and cord com- pression (a–c). The patient was selected for a posterior approach. After careful intubation under endoscopic guidance, partial spinal alignment was obtained by positioning the patient on the operating table with high skull traction and neck extension ( d). Cord decompression was obtained by laminectomy of C1/C2 and enlargement of the foramen magnum. Occipitocervical fixation was performed using a screw/rod system from the occiput down to C4 ( e–g). The patient died 1½ years after surgery with preserved neurologic conditions and free of neck pain. Spinal Metastasis Chapter 34 989 abc Figure 5. Treatment of thoracic vertebral body metastasis a, b A 74-year-old man with multiple myeloma and T7 pathological fracture with cord compression. c Anterior resection of the T7 vertebral body and the adjacent discs was carried out before spinal reconstruction with a cage and a screw/rod fixation system. terior longitudinal ligament typically bulges into the defect created between the intact vertebral bodies. It should be removed to allow a complete excision of all the tumor that has infiltrated into the spinal canal. The reconstruction of the ver- tebral body is obtained using bone cement or a special reconstruction cage. Bone graft is only indicated in caseswith a long life expectancy. However, bone integra- tion may be a problem in cases with postoperative radiotherapy. Spinal stabiliza- tion is completed with an anterior plate and screw system to obtain solid spinal reconstruction ( Fig. 5). Metastatic lesions localized in the upper thoracic spine are more difficult to address using an anterior approach. A sternotomy is sometimes required and this particular surgery should be performed only in patients with long life expec- tancy [3, 35, 38]. Posterior transpedicular vertebrectomy is a valid alternative for tumors in the entire lumbar and thoracic spine The technique of posterior transpedicular vertebrectomy (Fig. 6) has been described as a valid alternative approach for tumors localized in the entire tho- racic and lumbar spine [1, 7, 8, 10, 24]. Using this technique, posterior cord decompression is obtained through a large laminectomy extended laterally to the costotransversal joints. The surgery is continued by performing the spinal instrumentation before the hemorrhagic phase of tumor resection. Pedicle screws are placed in the adjacent vertebrae, usually one level above and one below. The procedure is followed by the complete resection of both pedicles using drill, curettes and pituitary rongeurs until exposure of both nerve roots. Follow- ing the pedicle structures, in an oblique inwards direction, a cavity is created in the vertebral body by piecemeal tumor resection. The vertebrectomy is progres- sively carried out as an eggshell procedure, taking care to leave the vertebral body cortex intact and avoid any injury with the anterior located segmental ves- sels. Using the same access and passing above and below the nerve root, the adja- cent discs are also resected. The vertebrectomy is completed by ventrally pushing and resecting the tissues left along the posterior longitudinal ligament. Care must be taken not to push against the cord. The reconstruction of the anterior column is obtained using methylmethacrylate pushed into the defect with a large 990 Section Tumors and Inflammation a b c d Figure 6. Single-stage posterior transpedicular vertebrectomy and circumferential reconstruction a For metastatic compressive fractures of the thoracic and lumbar spine in a patient with fair general health and/or multi- ple metastases, an accepted approach is a vertebrectomy and reconstruction through a single-stage posterior transpedi- cular approach. b Pedicle screw instrumentation of the vertebrae above and below is first performed. The posterior decompression includes complete laminectomy, cord decompression, facet joint resection and pedicle removal on both sides. Careful piecemeal vertebrectomy and resection of the two discs is performed from posterior using curettes and pituitary rongeurs. c At this point, the previously inserted instrumentation is used to realign the spine. d The vertebral body is reconstructed using bone cement, which can be finally compressed by the instrumentation in order to obtain solid fixation. syringe. The definitive posterior instrumentation is then completed connecting the previously inserted pedicle screws with two lateral rods ( Case Study 2). This technique may be less effective in the radical resection of the metastatic lesion but has been described as less invasive for the patient who does not require post- operative ICU recovery and can be immediately mobilized without external sup- Spinal Metastasis Chapter 34 991 . function, radiographic changes) and results of treatment for patients with spinal metastases. As the treatment of malignant diseases advances and the percentage of patients developing symptomatic. on: general health status of the patients neurologic conditions primary site of the cancer number of spinal metastases existence of extraspinal bone metastases involvement of major internal organ. points) and there- fore the indication for surgical management for each patient with spinal metasta- sis. 984 Section Tumors and Inflammation Non-operative Treatment The treatment of symptomatic spinal