Mehmet S. Copur, MD, and colleagues examine the case of a 65-year-old who presented with back pain and a large T8 spinal mass, leading to a diagnosis of multiple myeloma with spinal cord compromise.
ABSTRACT: Spinal cord compression is a potentially devastating consequence of cancer. Early recognition of the signs and symptoms permit diagnosis prior to the development of irreversible neurological damage. This complication occurs in 5% to 10% of patients with malignancy, often at the end stages of the patient’s illness; however, it can be the presenting manifestation of malignancy in up to 23% of patients. With the advances in surgical, radiation, and medical oncology approaches, the outcomes of patients with malignant spinal cord compression continue to improve. We discuss the case of a previously healthy man, aged 65 years, who presented with back pain and a large T8 spinal mass, leading to a diagnosis of multiple myeloma with spinal cord compromise.
Spinal vertebral bone involvement with or without neurological deterioration can occur as a skeletal-related event in various cancers. The true incidence of malignant spinal cord compression is not known, but the estimate is about 15% in patients with advanced cancer.1 Metastases to the spine occur most commonly in patients with breast, prostate, and lung cancer, followed by those with renal, gastrointestinal, and thyroid cancer and malignant melanoma.2 Multiple myeloma is among the most common hematological malignancies leading to this complication. The spinal cord compression may present as a primary tumor (solitary plasmacytoma) or as part of the systemic involvement of multiple myeloma.3-5 Direct tumor extension into the vertebral column or the collapse of a vertebral body that contains metastatic disease can lead to the compression of the spinal cord. Initially, this causes reversible edema, venous congestion, and demyelination, followed by vascular injury and cord necrosis. With prolonged compression, permanent neurological damage occurs. Appropriate treatment of malignant spinal cord compression is complex and requires a multidisciplinary team approach.
Regardless of the tumor histology causing the spinal cord compression, the 3 most widely utilized treatment modalities have been surgery, radiation therapy (RT), and the administration of glucocorticoids, with or without systemic anticancer therapy. The introduction of new spinal instrumentations and surgical approaches, along with advances in radiation and medical oncology treatments, has considerably improved the extent of therapeutic options, resulting in better outcomes. Identifying the patients who would most benefit from what initial approach—surgical, radiation, or medical treatment—is the most crucial part of appropriate management.
A man aged 65 years presented with right-sided lower thoracic back pain of 1-month duration; it was brought upon by pushing a sliding door in his garage. While it was initially a sharp pain, it transformed into a dull continuous ache radiating to his right rib and right hemithorax. He thought he pulled a muscle and saw a chiropractor, but he received no relief despite 5 chiropractic treatment sessions. During all this time he did not notice any extremity weakness or bladder or bowel incontinence, but he eighth area. He next saw his primary care provider, and a CT scan of his chest revealed a soft tissue mass measuring 6.2 x 3.5 x 2.8 cm in the posterior mediastinum/posterior chest wall with involvement of the posterior eighth rib and adjacent T8 vertebral body, with extension into the right aspect of the spinal canal (Figure 1). Further evaluation with an MRI of the thoracic spine confirmed the T8 compression and associated soft-tissue mass causing moderate-to-severe central spinal stenosis (Figure 2). A CT-guided biopsy of this large destructive mass revealed sheets of plasma cells (Figures 3 and 4). Further work-up revealed abnormal serum protein electrophoresis with a 3.53 g/dL monoclonal serum paraprotein, abnormal serum immunoglobulins (Ig; 5365 mg/dl; IgA, 23 mg/dL; IgM, 11 mg/dL), abnormal free light chains (λ free light chain, 14.6 mg/L; λ free light chain, 146.2 mg/L; ratio, 0.1), and abnormal λ-2 microglobulin of 4.9 mg/L. Bone marrow aspiration and biopsy revealed plasma cell myeloma comprising 40% of marrow cellularity (Figures 5 and 6). Staging work-up was completed with a PET-CT, confirming large osseous destructive mass at T8 level (Figure 7).
Malignant spinal cord and/or cauda equina compression is a relatively common complication of malignancy. While it is most common in the late stages of cancer, it can be the first manifestation of malignant disease. Depending on the extent and location of the spinal cord involvement, patients may present with various symptoms and signs, ranging from pain and motor and/or sensory loss to paraplegia and urinary or fecal incontinence. Long-term neurological functioning closely correlates with the patient’s mobility at the time of initial presentation. Patients with established spinal cord compression classically exhibit bilateral upper motor neuron findings below the level of the compression, but unilateral findings can also be seen. A circumferential sensory level below which sensation is reduced or altered may be noted. Bowel or bladder dysfunction can be present. In some cases, loss of balance may be the main presenting symptom due to compression of the posterior spinal cord.6,7
The goals of treatment for spinal cord compression are adequate pain control, relief of spinal cord or cauda equina compression, and maintenance of spinal stability, while preserving or improving neurologic function. After the immediate administration of glucocorticoids in nearly all patients, the choice of initial treatment modality depends on several factors, including the presence or absence of spinal instability, the degree of compression of the spinal cord, and the relative radiological and/or chemotherapeutic sensitivity of the tumor.8,9
An expert opinion consensus classification system for spinal instability has been developed based on the available evidence about patient symptoms and radiographic criteria.10 This classification uses 6 individual components of spinal instability: spinal location of the tumor, presence and character of the pain, nature of bone metastases, radiographic spinal alignment, extent of vertebral body involvement, and extent of posterior spinal element involvement. All of these are scored to create a final composite Spine Instability Neoplastic Score (SINS) (Table 1).11 In guiding the operative vs nonoperative management of patients with neoplastic spinal cord compression, SINS has been shown to be useful, with very good interobserver agreement among radiologists and radiation oncologists.12,13 According to this classification system, patients with a score of 7 or higher are considered to be at risk for spinal instability. The most appropriate treatment modality for an unstable spine is stabilization either by surgery with fixation14 or by percutaneous vertebral repair.15 RT and spinal bracing have not been shown to be effective for this group of patients.16,17
A life expectancy of at least 3 months and neurologic function compromise of less than 24 hours have been utilized as indicators for surgical candidacy.18 Patients with hematologic malignancies should be excluded, as they are best managed by RT or chemotherapy. Surgical intervention is performed to accomplish mechanical stabilization, pain relief, preservation of neurological function, and local tumor reduction. Although various surgical approaches can be used, the majority of cases have historically been managed by decompressive pressive posterior laminectomy. However, without instrumentation, decompressive laminectomy has been associated with a failure to resolve anterior compression as well as to cause or exacerbate spinal instability. A stand-alone laminectomy is considered only for metastatic involvement of the epidural space and lamina.
Additionally, the choice of surgical approach—anterior, posterior, or circumferential—is determined by the affected region of the spine. Metastatic spine lesions occurring ventrally in the subaxial cervical spine are best approached anteriorly. For thoracic spine lesions, transpedicular approaches are preferred, because an anterior approach can be challenging due to mediastinal contents. The transpedicular corpectomy and costotransversectomy can provide the added benefit of ventrally decompressing the spinal cord or thecal sac. Costotransversectomy involves more extensive resection and bone removal by providing better access to the anterior spinal column from a more lateral route.19-21 Modern surgical techniques and the development of spinal implants composed of high-quality materials, such as titanium, have significantly improved outcomes.
Prospective evaluations of RT plus laminectomy without instrumentation have not shown any benefit for this combination compared with RT alone.22 Data from prospective cohorts demonstrate that laminectomy combined with instrumentation for stabilization could improve neurological outcomes and pain.23,24 However, these prospective studies do not have control groups, so conclusions are limited. In a select group of patients, surgery followed by RT is a beneficial treatment when compared with RT alone. In a randomized trial, patients with single-level disease, good performance status, and an onset of symptoms within 24 hours were treated with either circumferential decompressive surgery followed by RT (30 Gy in 10 fractions) or RT alone. Analysis showed a clear difference in the number of patients who were able to walk 4 steps post treatment, as well as higher rates of continence and better muscle strength and functional ability, with less need for opioid analgesics and corticosteroids.25 Patients who are not candidates for radical surgery but who have an unstable spine may benefit from minimally invasive techniques such as vertebroplasty and kyphoplasty. Percutaneous vertebroplasty is performed by the percutaneous placement of 1 or 2 trocars into the vertebral bodies through the pedicles, or by the extrapedicular approach and the injection of methylmethacrylate under fluoroscopic guidance. Balloon kyphoplasty is a modified version of percutaneous vertabroplasty; it utilizes an inflatable balloon in a fractured vertebra to create a cavity into which the cement can be injected.26,27
In the absence of compression fracture or instability, external beam RT (EBRT) is also an effective treatment option for patients with significant comorbidities and limited life expectancy. RT is an indispensable part of adjuvant treatment following spine surgery when it was not possible to obtain wide surgical margins. To avoid adversely affecting wound healing, RT should be given 1 to 3 weeks after surgery.28 RT schedules need to be individualized, and efficacy is highly dependent on histology. In general, patients with solid tumors, such as breast and prostate cancers, are moderately radiosensitive, while patients who are mostly radioresistant include those with cancers such as melanoma, osteosarcoma, and thyroid, colon, and renal cancers. RT alone is frequently utilized in patients with such hematological malignancies as lymphoma or myeloma due to the sensitivity of these tumors to RT.29 In a systematic review involving 7 retrospective studies with 885 patients, RT provided a mean local disease control rate of 77%.29 In a meta-analysis involving 543 patients, a pain control rate of 54% to 83% was reported with the use of RT.30
No standard RT regimen exists for the treatment of malignant spinal cord compression. For patients with painful bone metastases, 1 to 5 low-fraction regimens with high single doses (4 to 10 Gy) have been shown to provide similar clinical outcomes to those of more protracted regimens.31-35 In a prospective, randomized, phase 3 trial, Maranazo et al randomized 300 patients to either a short-course (8 Gy x 2 days) or split-course (5 Gy x 3 days or 3 Gy x 5 days) schedule. At a median follow up of 33 months (range, 4-61), both regimens of hypofractionated RT were effective, with no severe adverse effects. Considering the convenience of the short-course regimen, the authors concluded that the short-course therapy could be the hypofractionated RT regimen of choice for patients with malignant spinal cord compression.36
With the advances in stereotactic RT techniques, this approach has been utilized to allow precise high-dose targeting in 1 or 2 fractions while minimizing exposure to the healthy surrounding spinal cord tissue.37 A systematic review involving 59 studies with 5655 patients treated with stereotactic RT for spinal metastases showed local control rates of 80% to 90% for patients with newly diagnosed disease, 80% for postsurgical patients, and 65% for previously radiated patients.38 Results from glucocorticoid therapy, RT, and surgical therapy trials of malignant spinal cord compression are summarized in Table 2.
Multiple myeloma is a clonal B-cell disorder characterized by malignant transformation and the proliferation and accumulation of postgerminal center plasma cells in the bone marrow and occasionally at extramedullary sites. The reported incidence of extramedullary disease in newly diagnosed multiple myeloma ranges from 7% to 18%, while 6% to 20% of patients may develop extramedullary disease later in their disease course.39 The outcomes of patients with multiple myeloma have significantly improved due to the widespread use of autologous stem cell transplantation (ASCT) and novel therapies targeting both the myeloma clone and its microenvironment. Control of bone disease in myeloma patients still represents a therapeutic challenge, however. At some time during their disease course, more than two-thirds of these patients present with osteopenia, osteoporosis, or pathological fractures, which frequently involve the spine and cause spinal cord compression.40
Treatment of spinal lesions in multiple myeloma requires a multidisciplinary approach. Prompt diagnosis and immediate treatment are critically important. Systemic therapy, including such modalities as chemotherapy agents, steroids, proteasome inhibitors, and immunomodulatory drugs, can be used in select patients with minimal risk of neurologic deficit. Surgical management of multiple myeloma–related vertebral lesions is seldom utilized due to this disease’s sensitivity to chemotherapy and RT. The rare indications for surgical intervention may include unstable fractures and spinal cord compression caused by bone fragments protruding from a vertebral fracture.41
The combination of EBRT and glucocorticoids is usually the treatment of choice for multiple myeloma patients who have impending vertebral fracture or spinal cord compression; it also provides pain control. EBRT also represents the treatment of choice for solitary plasmacytomas.42,43 Early studies that were conducted in small patient cohorts demonstrated that pain relief, quality of life, and motor function were improved in a sizable proportion of treated patients.44,45 No differences in general efficacy or in the extent and rapidity of pain relief have been observed using a fractionated 2-week course of 30 Gy vs a single fraction of 8 to 10 Gy.46 The radiation field should be large enough to compensate patient motion but as limited as possible to preserve marrow function. This is especially true for patients who are candidates for ASCT, because peripheral blood stem cell collection can be impaired when RT is applied in large fields.47
The patient was evaluated by neurosurgery, medical oncology, radiation oncology, and interventional radiology specialties in a multidisciplinary fashion. The SINS was calculated to be 4. He was started on oral dexamethasone along with EBRT to his spinal disease. He received a total of 20 Gy (5 daily fractions of 4 Gy each). Upon completion of his EBRT, he was started on a lenalidomide, bortezomib, and dexamethasone (RVD) regimen. Within the first week of his radiation treatment, he reported a 90% decrease in spinal pain. Five weeks after the start of EBRT, a repeat MRI of the spine showed a significant decrease in spinal mass (Figure 8). Following 2 cycles of RVD, a very good partial response was achieved. After the completion of 4 cycles of RVD, he will be undergoing ASCT with high-dose melphalan chemotherapy.
FINANCIAL DISCLOSURE: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
Copur and Zusag are from the Morrison Cancer Center, Mary Lanning Healthcare, Hastings, Nebraska.
Bell is from the Inspired Brain and Spine Surgery, Mary Lanning Healthcare, Hastings, Nebraska.
Rodriguez is from Diagnostic Radiology, Mary Lanning Healthcare, Hastings, Nebraska.
Wedel and Lintel are from the Pathology Department, Mary Lanning Healthcare, Hastings, Nebraska.
Allan is from Midwest Imaging Interventional Radiology, Grand Island, Nebraska
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