Treatment of Spinal Metastatic Tumors

Published on 12/03/2015 by admin

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Chapter 26 Treatment of Spinal Metastatic Tumors

Ilya Laufer, Marcella A. Madera, Daniel Sciubba, Ziya L. Gokaslan

Clinical Pearls

• Histology plays paramount role in determination of tumor treatment. After a thorough radiological evaluation of the extent of systemic and spinal disease, a percutaneous computed tomography–guided biopsy is frequently the next step in the diagnostic algorithm, because 10% to 20% of the spine metastases have no known primary source. Determination of tumor histological type is of critical importance in determining the appropriate subsequent treatment.

• Treatment of metastatic spine tumors optimally requires a multidisciplinary approach that involves surgeons, radiation and medical oncologists, radiologists, and rehabilitation medicine physicians. However, the general treatment goal of patients with spinal metastases is palliation, because spinal metastases usually signal advanced metastatic disease with little hope of cure. Mechanical instability and high-grade cord compression secondary to solid tumors may require surgical decompression and stabilization as part of the palliative plan as long as survival time anticipated from the systemic neoplastic disease is greater than 3 months.

• The choice of surgical strategy and approach for spinal metastases remains predicated on the surgeon’s comfort, training, and experience. The definition of mechanical instability in patients with metastatic spinal tumors has recently been elucidated by an expert panel. The same stability classification used in trauma should not be applied to metastatic cases. Movement-related pain or pain relieved with recumbence may be considered to be a symptom of instability. Lytic lesions, subluxation and progressive deformity, extension into the posterior elements, and lesions that occupy more than 50% of the vertebral body and are accompanied by loss of height are also judged to be associated with instability. These symptoms and signs of instability and progressive neurological compromise may lead the treatment team to recommend surgical stabilization.

• When a ventral surgical approach for decompression and stabilization is employed, an anterior plate spanning one level above and one level below the vertebrectomy defect is generally used in order to buttress the cage or cement reconstruction. In posterior decompression, lateral mass or pedicle instrumentation is usually employed, spanning at least two levels above and below the tumor.

• Stereotactic spinal radiosurgery may provide excellent tumor control rates in radioresistant tumors. Radiosensitive tumors, such as lymphoma, multiple myeloma, plasmacytoma, and small cell lung carcinoma may be treated with radiation therapy even in the presence of cord compression.

Physicians will make over 1.5 million new diagnoses of cancer in 2010 in the United States, and over 500,000 people are expected to die from cancer in 2010 [fact sheet 2010]. Five-year survival rates in patients with cancer have improved to 68% (1999-2005) from 50% (1975-1977) as treatment techniques have advanced [fact sheet 2010]. Spine metastases, the most common site of bone metastasis, occur in 30% to 90% of terminal cancer patients.¹^–³ As patients continue to live longer with cancer, it is likely that spine metastatic disease rates will continue to climb.

The most common primary tumors that give rise to spine metastases are breast, lung, and prostate cancers, reflecting the high prevalence of these tumors.³ These primary tumors may spread to the spine through the arterial or venous systems, by direct extension, or via cerebrospinal fluid (CSF). Hematogenous spread (arterial or venous) is thought to be the most common route by which primary tumors metastasize to the spine. Because the vertebral bodies have an extensive arterial blood supply, tumor cells from distant primary lesions can travel to the spine and initiate metastatic disease.⁴ Venous spread occurs by flow through Batson’s plexus, the longitudinal network of valveless veins that connects vertebral veins with many venous beds (caval, portal, azygous, intercostal, pulmonary, and renal). Primary tumors may also spread by direct extension; lung cancer can extend posteriorly to the thoracic spine or superiorly to the cervical spine. Pelvic or abdominal cancers (prostate, bladder, and colorectal) can locally invade the lumbar or sacral spine. Metastasis through the CSF can occur spontaneously or after surgery for brain lesions. Multicentric disease (i.e., tumor in multiple vertebrae) can result from any of these mechanisms of spread.

The location of spine metastases may be extradural, intradural-extramedullary, and intramedullary, with most occurring in the extradural space. This spread is usually in the vertebral body and may include extension to the posterior elements. The extradural compartment also includes the epidural space and paravertebral space, both of which can contain tumor as it extends from bone. The most common levels for spine metastases, in descending order of frequency, are the thoracic, lumbar, cervical, and sacral regions of the spine. Intradural metastases, whether intra- or extramedullary, are very rare but result from spread through the CSF.

Presentation

Metastatic tumors can cause any neurological or structural symptom associated with spine pathology in general. The spine not only protects the neural elements but also provides mechanical support to the body. Pathology in the spine can affect either or both of these basic functions of the spine. Loss of integrity of the spine due to metastasis may cause the patient back pain, radicular pain, paresis, paralysis, numbness, bowel or bladder dysfunction, myelopathy, fractures, or spinal deformity. In addition to spine-related symptoms, patients with metastatic disease may have global symptoms such as weight loss, fatigue, and other organ system abnormalities.

Pain

Pain, the most common first presenting symptom of spine metastasis, can have different mechanisms depending on the tumor’s interaction with the bony spine or the neural elements, and 83% to 95% of patients with spinal metastases complain of pain. Because pain often precedes other neurological symptoms, it should be carefully evaluated by clinicians.^5,⁶ If tumor compresses a nerve root, pain that is burning and radiates down the leg in a dermatomal distribution (radicular pain) is a common symptom. If tumor causes a pathological fracture or collapse of a vertebral body, that collapse can narrow the foramina and cause radicular pain, or it may cause mechanical pain. Mechanical pain typically is worse with loading of the spine during sitting or standing, and it often does not improve with anti-inflammatory medications. Local or biological pain may also be experienced by patients with spine metastases; it is usually described as a deep ache that is worse at night. This type of pain can improve with anti-inflammatory medications or corticosteroids, and it is likely due to inflammation in the spine due to the presence of tumor. Tenderness to palpation over the spine may be evident on physical examination due to local pain from periosteal stretching and inflammation. Treatment of spine metastases often includes a goal of treatment of the patient’s pain, and the type of pain a patient experiences may guide that treatment. Local pain is often palliated with radiation treatment; mechanical pain may be best addressed with bracing or surgical stabilization.

Neurological Dysfunction

The second most common group of symptoms that patients with spinal metastases complain of is neurological deficit.⁷ Weakness in upper or lower extremities may result from epidural compression of the spinal cord, individual nerve roots, or the cauda equina by tumor. Tumor or fractured bone fragments may impinge on neural structures, and patients may also complain of autonomic problems including bowel, bladder (usually urinary retention), or sexual dysfunction. Asking patients directly about these problems should be routine, as the symptoms might not be revealed on initial history gathering. Without treatment, motor dysfunction usually progresses to paralysis. Dermatomal changes in sensation, including anesthesia, hyperesthesia, and parasthesia, usually occur with motor dysfunction and pain. Patients with spinal cord compression may complain of sensory abnormalities in a band-like distribution across the chest or abdomen. Myelopathy also results in hyperreflexia from chronic spinal cord compression. Diagnosis before these neurological deficits occur is important because neurological prognosis is related to the amount of neurological function at the time of diagnosis.⁴ Pain is usually experienced before a neurological deficit, but because of the extremely common prevalence of back pain in the general population, metastatic spine disease can be missed until deficit occurs. Any patient with a known history of cancer and a new complaint of back or neck pain should be thoroughly evaluated for spinal metastatic disease. As the thoracic spine is the most common location for metastasis to the spine, and degenerative problems there are less common, pain in the thoracic spine should cue clinicians to consider a neoplastic process in patients with new-onset thoracic pain.

Diagnosis

Patients with a newly diagnosed spinal lesion require a thorough diagnostic workup, which begins with a history and physical examination. Patients without cancer diagnosis require a standard evaluation and management of back pain, which would likely include initial observation and conservative treatment without extensive imaging or invasive diagnostic procedures. However, certain signs and symptoms may increase the probability of a neoplastic process and merit a more aggressive initial evaluation. Fatigue and unintended weight loss may result from a systemic process such as cancer. Furthermore, history of human immunodeficiency virus (HIV), chronic inflammatory conditions, smoking, hazardous occupational exposures, and familial cancer history increases the likelihood of a neoplasm. Nocturnal or morning back pain elevates the suspicion for neoplasm, and progressive pain during the course of the day is generally more indicative of degenerative lesions. In patients with a previous diagnosis of cancer, any back pain or neurological deficit should prompt a diagnostic evaluation in order to determine if the patient harbors any metastatic lesions. Prior to any decision regarding treatment, a thorough oncological staging evaluation must be performed according to the histology-specific protocols. Hematological, electrolyte, endocrinological, and cancer marker aberrations may aid in the diagnosis of tumor histological type and stage.

Imaging Studies

Plain radiographs often serve as an initial imaging evaluation of a patient with back pain, owing to their low cost and widespread availability. These studies may help in identifying significant abnormalities such as compression fractures, scoliosis, large lytic or sclerotic osseous lesions, and radiopaque extraossous lesions. However, in order to be apparent on plain radiographs, the lesions must reach a significant size, thereby making these studies a fairly insensitive modality in tumor diagnosis.⁸ Although radiographs may be an appropriate initial study in patients without history of cancer, they should not be used as a screening or diagnostic modality in patients with an elevated suspicion of spine tumors.

Multidetector computed tomography (CT) scanners provide a rapid high-resolution image of the spine and surrounding structures. The availability of two- and three-dimensional reconstructions allows easy localization and visualization of lesions that are hyper- or hypodense in relation to the surrounding structures. The lesions appear lytic, sclerotic, or mixed and this information may aid in the determination of the potential stability of the spine. The great definition of the osseous anatomy also aids in operative planning, allowing precise measurements of the screw length and diameter suitable for each vertebral body, as well as the trajectory of the screw insertion. CT imaging is also invaluable in imaging instrumentation position and the degree of osseous fusion. Finally, injection of dye into the subarachnoid space during CT myelography allows precise definition of the CSF surrounding the cord and nerve roots. This technique is invaluable in diagnosing neural element compression in the setting of instrumentation that creates ferromagnetic artifact on magnetic resonance imaging (MRI) or in patients who cannot undergo MRI. It has become a standard component of treatment planning for spine stereotactic radiosurgery in patients with spinal hardware.

Universal nuclear body scans have become a standard component of histological staging for certain cancers. Nuclear scintigraphy (bone scan) permits detection of osseous remodeling throughout the skeletal system and has been reported to have 62% to 89% sensitivity in detection of spinal metastases.⁹ However, it is not specific for neoplasms and cannot differentiate tumors from regions of infection and inflammation. Furthermore, in order for a neoplasm to be detected on a bone scan, active osseous remodeling must be taking place, which is not always the case in sclerotic neoplasms. Single-photon emission computed tomography (SPECT) permits improved differentiation of neoplastic from inflammatory processes, because it detects the metabolic components of the lesion.^10,¹¹ It allows three-dimensional imaging of the lesion with sensitivity and specificity superior to standard bone scans. Finally, positron emission tomography (PET) using fluoride-18 (¹⁸F-PET) and ¹⁸F-fluorodeoxyglucose (¹⁸FDG-PET) provides a sensitive screening modality for neoplastic lesions through the body. ¹⁸F-PET detects regions of fluoride uptake and thereby skeletal remodeling. ¹⁸FDG-PET detects regions of high glucose uptake in the skeletal system and the soft tissues, thereby detecting hypermetabolic lesions that may signify a neoplastic, degenerative, inflammatory, or infectious process. However, correlation with concomitant MRI and CT scans generally allows high diagnostic specificity. Furthermore, ¹⁸FDG-PET has been shown to be a highly sensitive and specific screening modality in patients with solid tumors harboring spinal lytic and mixed lesions.¹² The decreased sensitivity of ¹⁸FDG-PET in detection of sclerotic lesions may be associated with the acellular and therefore low metabolic nature of these lesions. PET imaging may also aid in the selection of biopsy targets in the setting of multiple lesions, because lesions with higher metabolic activity will likely produce higher diagnostic yield due to their high cellularity.

MRI remains the gold standard in spine imaging and in detection of spinal metastases. MRI has superior sensitivity and specificity in screening for vertebral metastases, allowing precise delineation of their size, quantity, and location. It furthermore provides thorough information about the surrounding soft tissues that include the spinal cord and nerve roots, ligaments, meninges, interverterbal disks, and paraspinal musculature. In addition to the standard T1- and T2-weighted sequences with gadolinium injection, fat suppression and diffusion-weighted sequences may provide additional information about the acuity and etiology of visualized fractures. MRI allows excellent visualization of the spinal cord and nerve roots and any compression that may result from epidural tumor extension. T2 hyperintensity of the cord signifies cord edema and may indicate increased severity of compression.

Percutaneous CT-guided biopsy is a frequent step in the diagnostic algorithm, because 10% to 20% of the spine metastases have no known source and determination of tumor histological type is of paramount importance in determining the appropriate treatment.¹³ Furthermore, in patients with distant cancer history a biopsy may be required in order to rule out a second malignancy. Modern large-bore needle biopsy techniques have excellent diagnostic yield and are generally performed as an outpatient procedure. Caution must be exercised when interpreting negative biospsies of blastic lesions, because they may be falsely negative owing to their acellular nature. Such patients may merit additional follow-up in order to monitor these lesions clinically and radiographically.

Metastases that originate from hypervascular primary tumors generally require preoperative digital subtraction angiography and embolization. Angiography allows evaluation of the vascularity and the blood supply of the tumor and delineation of the location of the artery of Adamkiewitz. Renal, thyroid, hepatocellular, neuroendocrine tumors and tumors that contain “angio” or “hemangio” in their name should generally undergo angiography and embolization when possible. Complete and even partial preoperative embolization of vascular tumors has been shown to significantly decrease intraoperative blood loss.¹⁴^–¹⁶