Management of Metastatic Spinal Disease

Abstract

Study Design

Narrative review.

Objective

This review presents a comprehensive approach to the management of spinal metastases.

Methods

N/A.

Results

The wide spectrum of clinical presentation in spinal metastases necessitates a personalized approach to treatment planning. This includes a comprehensive diagnostic workup, oncological management, palliation of symptoms, and surgical intervention if appropriate. A systematic and multidisciplinary approach allows optimal shared decision making to reach an evidence-informed and value-congruent treatment plan for the patient. We highlight how advances in stereotactic body radiotherapy (SBRT) and separation surgery may be incorporated into clinical management from a spine surgeon’s perspective.

Conclusion

This review summarizes the approach and management of spinal metastases, its outcomes and complications.

Keywords

spinal metastases multidisciplinary approach management SBRT

Introduction

Patients suffering from bony metastasis are presenting with greater frequency to the spine surgeon. The past decades have seen a rising incidence of cancer, as well as rapid advances in personalized medicine.¹ An improvement in survivorship as well as the introduction of separation surgery followed by stereotactic body radiotherapy (SBRT) has a led to a paradigm shift in the management of metastatic spinal disease. Patients should be individually evaluated by a multidisciplinary team comprising of spine surgeons, medical oncologists, radiation oncologists, interventional radiologists, and allied health practitioners towards formulating evidence-informed and value-congruent management plans.

Epidemiology

The bony skeleton represents the third most common site of tumour metastasis overall, after the lung and liver. The overall occurrence of osseous metastasis is 30% in patients with cancer.² A recent meta-analysis on metastatic spinal disease identified commonest sites of primary tumour pathology to be originating from the lung (30.7%), kidney (17.7%), breast (15.9%), prostate (14.1%), hepatobiliary system (3.6%), thyroid (3.4) and colorectal region (1.6%).³ In patients younger than 20, endocrine cancers and soft tissue sarcomas are a common culprit.⁴ Cadaveric studies have demonstrated metastatic spinal disease, which is often subclinical and undetected, in up to 90% of patients. Spinal metastasis is 20 more times common than primary tumours, has a peak incidence of 40–65 years of age, and has a male predominance.⁵ Approximately 50% of osseous metastases involve the spine.² Metastatic epidural spinal cord compression (MESCC) occurs when epidural tumour components displace the spinal cord, and is estimated to occur in up to 10% of cancer patients.⁶

Pathophysiology of Spinal Metastasis

Metastasis occurs as cancer cells detach from the primary tumour, enter the bloodstream, invade and survive within distant tissue sites following molecular interactions between tumour cells and target tissues.⁷ Juxtacrine cell signalling between tumour and immune cells facilitates immune evasion and tumour proliferation.⁸ Bony destruction and loss of physiological marrow function follows,⁹ which together incite skeletally-related events. Skeletally-related events (SREs) require prompt clinical management and include pathological fractures, tumour-induced hypercalcemia, and spinal cord compression.

The thoracic spine is most commonly affected in spinal metastases (70%), followed by the lumbosacral (20%) and cervical spine (10%). Bony metastases most commonly result from hematogenous spread. Bone marrow is highly vascular, and this predisposes to seeding within the vertebral body.⁵ The Batson’s venous plexus connects thoracic and pelvic veins to the internal vertebral venous plexus and is unique in being valveless thereby representing a pathway by which metastasis occurs.¹⁰ The preference of different primary tumours to metastasize to specific regions along the spinal column may also be explained by their venous drainage. Thoracic vertebrae are commonly affected by metastases from lung and breast cancers via drainage from the azygos vein. On the contrary, prostate cancer commonly metastasizes to the lumbar spine via the pelvic venous plexus.¹¹

Spinal cord compression results when bony metastases destroy cortical bone to cause retropulsion or instability, and when tumour tissues extend into the epidural space.^12,13 Mechanical compression of the spinal cord disrupts arterial and venous circulation.¹⁴ Prolonged compression results in cord ischemia, tissue infarction, and irreversible neurological deficits.¹⁵ The CSF also presents a medium for tumour migration. Disseminated tumour cells within the subarachnoid space may spread as drop metastases to encase the spinal cord and nerve roots.

Presentation of Metastatic Spinal Disease

Vertebral metastases are asymptomatic upon diagnosis in approximately 40% of patients.¹⁶ Patients with symptomatic vertebral metastasis most commonly present with back pain (exhibited in over 80% of individuals).^17,18 ‘Red flag signs’ consistent with tumour include rest pain and night pain, associated with constitutional symptoms such as anorexia and weight loss.¹⁹ Nevertheless, there is a median delay of 8-weeks between the onset of back pain and a formal diagnosis of metastatic spinal disease.¹⁴ Spinal metastases cause pain from vertebral destruction, invasion of the periosteum, and compression of neural elements.²⁰ Neurological deterioration is often preceded by pain for weeks to months.²¹ It is therefore critical that back pain due to spinal malignancy is recognized early.

Encroachment of the spinal canal by tumour tissue results in neurological symptoms and signs that are specific to the region of vertebral column involvement. Rates of motor weakness upon presentation have been reported to range from 35 – 85%, and sensory disturbance at 60%.²² The loss of ambulation is ominous, foreboding a median survival of 1.5 months in comparison to 7 months in walkers.²³ Autonomic dysfunction may also occur and cause loss of bladder/bowel control and sexual dysfunction.

Diagnostic Workup

Imaging

The objectives of imaging are to facilitate diagnosis of spinal metastasis, and to assess the local and systemic extent of involvement.²⁴ Plain X-rays are useful for evaluation of overall spinal alignment, instability, and bony destruction, but only reveal lesions of >1 cm with >50% loss of mineralization.²⁵ More than 50% of patients have spinal metastasis at multiple levels, and of these 10 – 38% have non-contiguous levels affected.²⁵ Therefore, an MRI scan of the whole spine is the investigation of choice for radiological diagnosis of spinal metastasis. Diffusion-weighted imaging sequences have excellent sensitivity and specificity in the detection of bony metastasis.²⁶ T2 sequences are useful in the assessment of compression upon neural elements and for the diagnosis of multiple myeloma.²⁷ The addition of contrast is useful to delineate epidural metastases, as well as detect vertebral osteomyelitis and epidural abscesses as differential diagnoses.²⁸

The utility of systemic imaging is for tumour staging towards prognostication and treatment planning. Bone scintigraphy allows for detection of metastatic foci throughout the bony skeleton, most commonly utilizing technetium-99m as a tracer to detect new bone formation. One must be aware of false negatives in the absence of reactive bone formation and vascular perfusion, in diseases such as multiple myeloma, anaplastic carcinomas, and prostate cancer.²⁵ Additionally, [¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scans have become widely available for systemic tumour staging. In combination with CT, FDG-PET scans exhibit a sensitivity of 98% in detecting spinal metastases.²⁵ A caveat for tumour detection via FDG-PET is in the detection of osteoblastic lesions with low glucose uptake. Other PET-negative solid organ tumours include certain lung cancers,²⁹ as well as hepatocellular carcinomas.

Surgical Biopsy

Biopsies allow for retrieval of tissue specimens towards confirming the diagnosis of spinal metastasis in relation to a known primary malignancy, or to identify the primary tumour when this remains uncertain. Percutaneous image-guided biopsies performed by an interventional radiologist may be preferred to open biopsies in being less invasive whilst possessing a diagnostic accuracy of approximately 90%.³⁰ One should be aware of the potential for local recurrence along the site of the needle tract, which should be marked for subsequent resection should there be any suspicion of a primary spinal tumour.³¹ Core biopsies are the standard of care in allowing for assessment of tissue architecture as well as cytogenic/immunohistochemical studies towards selection of systemic treatment. General principles towards selecting biopsy sites include targeting larger lesions that are superficial and away from neural/vascular elements, as well as targeting lytic before sclerotic lesions. Depending on the lesion location, transpedicular approaches (suited for lesions located centrally), and transforaminal/paraspinal approaches (suited for lesions located laterally) may be utilized.³² In the clinical context of cord compression mandating urgent surgical decompression, histological specimens are obtained intra-operatively.

Clinical Decision-Making

Treatment objectives include palliation (ie of underlying pain, and preservation of neurological function), disease control, or providing a chance of cure. In surgical candidates, objectives include decompression of neural elements, clearance or debulking of tumour tissues, and stabilization of the spine. Comprehensive assessment of patient and disease factors by the multidisciplinary team facilitates formulation of a personalized treatment plan. We review patient and disease factors essential for clinical decision making here. The overarching NOMS framework introduced by the Memorial Sloan-Kettering Cancer Centre is discussed in a subsequent section on stereotactic body radiotherapy.

Overall Prognosis

A number of scoring systems with reference to tumour histology have been described by Tokuhashi, Tomita, Sioutos, van der Linder, and Bauer³³ but in the era of personalized medicine these have been rendered obsolete. Oncologist input remains invaluable in gauging life expectancy. Surgery should only be offered should there be reasonable survivorship (>6 months), patient fitness, and oncological modalities available for systemic disease control.³⁴ The Karnofsky performance score (KPS) and ECOG score is commonly utilized to assess functional performance and remains useful in estimating survivorship, risk of surgical complications, and post-operative ambulatory status.³

Disease Burden and Localization

Curative resection may be feasible in solitary spinal metastasis or oligometastatic disease after considering the anatomical location of tumour tissues as well as patient fitness.³⁵ Conversely when there are multiple visceral in addition to spinal metastasis, palliative treatment is favoured.³⁴ Relating to overall disease burden is extent of metastatic involvement along the spinal column. Whilst localized metastatic epidural spinal cord compression may be amenable to surgery, diffuse, multi-level involvement often renders surgical treatment futile. Intramedullary and leptomeningeal metastasis are associated with particularly poor oncological outcomes and may be better suited to receive palliative radiation unless lesions are solitary.³⁶

Mechanical Instability

The spinal instability neoplastic score (SINS) provides a systematic framework to assess for mechanical instability based on location and extent of the metastatic lesion, mechanical pain, lytic/blastic nature of the lesion, spinal alignment, and vertebral body collapse.³⁷ The presence of mechanical instability signifies a necessity for surgical fixation in patients that are surgically fit and have a reasonable life expectancy. Vertebral augmentation is an alternative option in patients with a fair overall prognosis.³⁴

Neurological Compromise

Metastatic spinal cord compression may result in permanent neurological deficit if not promptly treated.⁵ Surgical decompression provides immediate mechanical relief and is the preferred option in high grade metastatic spinal cord compression. Time is of the essence as studies have indicated that neurological outcomes are significantly better when surgery is performed within 48 hrs after developing neurological compromise,³⁸ and some studies advocate surgery within 24 hrs.³⁹ An additional objective in prompt surgical decompression is to salvage sphincter function, which preserves patient independence, mobility, and dignity, as well as reduces caregiver burden. Upfront radiotherapy is indicated for palliation, and 29% of patients are still able to regain walking ability as compared to 64% of those receiving surgical decompression.⁴⁰

Medical Management of Metastatic Spinal Disease

Oncological Treatment of the Primary Tumour

Non-operative management directed by oncologists remains the backbone of treatment to achieve disease control or cure. Chemotherapy may be used as monotherapy for particularly chemosensitive tumours (ie lymphoma, seminoma), but most often is used in combination with other treatment modalities.⁴¹ With regards to radiotherapy, malignancies have historically been classified into being radiosensitive or radioresistant,⁴² yet stereotactic body radiotherapy (SBRT) has been able to delivery ablative treatment doses to conventionally radioresistant tumour types to achieve local control. Molecular targets have been identified for the systemic treatment for many different tumours, with examples of such therapeutic agents being tyrosine kinase inhibitors, aromatase inhibitors, anti-VEGF antibodies, and MAPK inhibitors.⁴³ These have revolutionized the management of solid organ tumours such as lung, breast, and colon cancer. Immunotherapy is a more recent development targeting the capacity for tumour cells to evade the immune system and has substantially improved upon the prognosis of metastatic renal cell carcinoma. Multiple myeloma affecting spinal vertebra respond very well to bisphosphonates and denosumab alone,⁴⁴ and radiotherapy for solitary plasmacytomas of the spine may similarly be curative.⁴⁵

Prevention of Skeletally-Related Events (SREs)

As bone targeting agents, both bisphosphonates and denosumab have proven efficacy in preventing SREs, with evidence supporting their use in metastatic lung, breast, prostate cancer, and multiple myeloma.⁴⁶ Zoledronic acid is a potent bisphosphonate most commonly administered as 4 mg intravenous doses every 3-4 weeks towards the prevention of SREs. Denosumab is a monoclonal antibody that attenuates osteoclastic activity and is given as a 120 mg dose subcutaneously every 4-weeks. Treatment should be initiated as soon as bony metastasis has been diagnosed.⁴⁷ Meta-analyses have demonstrated that denosumab may be better than bisphosphonates in preventing SREs,⁴⁷ but no difference was found between the 2 drug classes in reducing the likelihood of spinal cord compression.⁴⁸

Tumour Pain

Metastatic bone pain is often severe, with 30% of patients reporting Brief Pain Inventory (BPI) scores of ≥7.⁴⁹ Pain arising from irritation of periosteal nerve fibers is deep-seated and ‘gnawing’ in nature. Radicular pain, related to compression of nerve roots, is classically described as being electric shock-like, stabbing or burning in nature. Pain that is worse with movement may signify the presence of mechanical instability. Opioids are a mainstay of tumour management,⁵⁰ with nausea, vomiting and constipation being common side-effects that may require adjuvant treatment. One should be aware of non-responders/poor responders, and the risk of accumulating toxic metabolites in renal impairment.⁵¹ NSAIDs are often used for management of cancer pain and have an additive effect on pain control together with opioids.⁵² Anticonvulsants and neuroleptics may be useful in patients suffering from neuropathic pain yet should not be used indiscriminately as a recent meta-analysis on the control of cancer pain with gabapentin or pregabalin in combination with opioids, in comparison to opioids alone, failed to demonstrate benefit.⁵³ Radiotherapy is very effective for the relief of bone pain, with up to 70% of patients experiencing benefit 1 – 2 weeks after treatment initiation.⁵⁴ Percutaneous vertebroplasty is an effective and minimally invasive palliative procedure which will be discussed as a surgical option.⁵⁵ The efficacy of psychological treatment and cognitive behavioural therapy has been established for pain control in cancer⁵⁶ and should not be neglected in a multidisciplinary treatment approach.

Corticosteroid Therapy

Corticosteroids are proposed to preserve neurological function in metastatic spinal cord compression by reducing tissue edema and decreasing capillary permeability.¹³ Guidelines from a recent meta-analysis support administration within 12-hours of neurological symptom onset, delivered via a 10 mg IV loading bolus followed by dosage of 16 mg per day delivered in 4 doses.⁵⁷ Higher doses have been advocated from preclinical studies due to a greater reduction in tissue edema. Nevertheless, clinical trials have established than an increased cumulative dosage of corticosteroids was associated with a significant increase in steroid-induced toxicity (75% in patients with dose >400 mg vs 13% with dose <400 mg).⁵⁸ Due to an increased risk of gastric bleeding or perforation, concomitant coverage with protein-pump inhibitors is advisable.⁵⁷ Definitive therapy should be initiated as soon as possible, and upon surgical decompression, steroids should be promptly weaned within 5 – 7 days.

Prevention of Venous Thromoboembolism

Patients with metastatic spine disease are at risk of venous thromboembolism (VTE) because of their hypercoagulable state and reduced mobility. The incidence of deep vein thrombosis upon pre-operative patients about to receive surgery for spinal metastasis has been reported to be 9.5%.⁵⁹ Amongst non-ambulatory patients, incidence increases to 24.4%. Recent orthopaedic guidelines have advocated for the use of chemoprophylaxis against venous thromboembolism in oncological spinal procedures during the peri-operative period,⁶⁰ with treatment initiation or resumption ideally within 48 hrs of surgery. Whilst there is lack of high-quality evidence to support a chemoprophylactic agent of choice, low molecular weight heparin is a reasonable first option given the body of evidence supporting its efficacy in preventing VTE following elective spine surgery⁶¹ as well as in spinal cord injury associated with motor paralysis.⁶² The incidence of symptomatic epidural hematoma following spine surgery has been reported to be 1.8%, and an increased risk may result from chemoprophylaxis.⁶⁰

Surgical Options for Metastatic Spinal Disease

Curative Resection

According to treatment principles described by Enneking, en bloc resections comprise of complete tumour removal contained within a resection margin of normal tissue.⁶³ Indications for en bloc excision include single solitary spinal metastasis without invasion into adjacent viscera/blood vessels, and in slow-growing primary tumours such as renal cell, thyroid, or breast cancer. Surgical morbidity is dependent upon anatomic factors such as tumour size and location, disease burden and patient co-morbidities. A total spondylectomy typically involves en bloc laminectomy with posterior instrumentation, followed by vertebrectomy and anterior column reconstruction.⁶⁴ This remain a major undertaking with significant blood loss, long operative time, and high complication rates.⁶⁵ Nevertheless, refinement in surgical technique is reducing morbidity,⁶⁶ and partial vertebrectomies may suffice with lesser vertebral involvement.³⁵ En bloc resections offer the best chance of surgical cure in primary spinal tumours,⁶⁷ and 1-year and 5-year disease-free survival in the management of metastatic spine disease of 62% and 38% has been reported in selected patients.⁶⁸ Neoadjuvant chemotherapy may be offered to improve upon the rate of cure.⁶⁹

Surgical Decompression and Fixation

Patchell demonstrated in 2005 with regards to neurological outcomes that direct decompressive surgery followed by postoperative radiotherapy was superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.⁷⁰ In spite of advances in stereotactic body radiotherapy (SBRT), prompt surgical decompression remains the treatment of choice in high grade epidural compression causing acute neurological deficits.³⁸ Surgical management may also be favoured in metastatic spinal disease having received prior irradiation and in tumours with radio-resistance. Whilst anterior approaches are associated with increased neurological recovery, posterior approaches are often preferred due to familiarity and reduced perioperative risks.⁷¹ Surgical fixation is indicated in the presence of mechanical instability, which may be due to tumour invasion, or from intra-operative bony removal to facilitate wide decompression and separation surgery. Titanium implants are prevalent and of greatest familiarity to spinal surgeons, nevertheless present a hindrance to reassessment scans due to imaging artefacts. As such, imaging-friendly implant materials such as carbon fiber – PEEK should be considered as overall survival of patients with spinal metastasis necessitates reimaging, and potentially, repeated surgical procedures in the event of local progression/recurrence.⁷²

Local Ablative Procedures and Vertebral Augmentation

Thermal ablation technologies present a minimally invasive means for the management of spinal metastasis. These methods are able to achieve palliation of pain as well as local tumour control.⁷³ Treatment indications includes tumours which are radioresistant and patients who have already received a maximal cumulative dose of radiotherapy.⁷⁴ Radiofrequency ablation (RFA) is perhaps most reported within the literature. In RFA, delivery of a high-frequency alternating current generates heat to cause thermal necrosis of tumour tissues. RFA is best utilized in vertebral metastases with no or minimal bony involvement so cortical bone remains as a barrier to undesired thermal injury, as well as in lytic as opposed to sclerotic lesions as the latter has greater impedance⁷⁵ thereby limiting tissue temperatures. Other modes of thermal ablation include cryoablation and microwave ablation.⁷³

Vertebroplasty and kyphoplasty may be offered for the relief of pain resulting from vertebral destruction⁷⁶ and in the treatment of spinal instability amongst non-surgical candidates.³⁴ Cement and vascular leaks are known complications that are infrequently encountered, and systemic complication such as pulmonary embolism resulting from cement emboli encountered in less than 2% of patients.⁷⁷ Care should be taken when there is destruction of the posterior vertebral wall, or an epidural soft tissue component, although these do not represent absolute procedural contraindications.⁷⁸

Stereotactic Body Radiotherapy and Separation Surgery – How do They Fit in the Spine Surgeon’s Armamentarium

Principles of SBRT

Stereotactic body radiation therapy (SBRT) allows for very high doses of radiation to be delivered to tumour tissues in a conformational manner, and in so doing achieve tumour ablation whilst minimizing damage to surrounding normal tissues via a steep gradient dropoff. Histological assessment of resected metastases demonstrate that tumour necrosis and reduction of vessel density occurs by 24 hrs,⁷⁹ and even in radio-insensitive lesions this results in a reduction in tumour volume of 65% at 2-months.⁸⁰ Conventional external-beam radiation (cEBRT) on the other hand is limited by toxicity to normal tissue and delivers lower non-ablative doses of radiotherapy with greater frequency. cEBRT requires less planning and its utility remains for palliation of patients with poor prognosis (ie < 6 months expected survival).^34,81 SBRT represents a highly advanced form of targeted external beam radiation that requires rigid immobilization and acquisition of a CT scan/volumetric MRI sequences to allows for dose contouring.⁸² Customized body moulding devices such as BodyFix minimize deviations in positioning to within 2-3 mm.⁸³ Although requiring longer pre-treatment preparation, radiation doses are hypofractionated and usually completed within 1-2 weeks.⁸⁴

Patient Selection

The NOMS framework (neurological, oncological, mechanical, systemic) provides a common language to individualize management of metastatic spine tumours especially with relation to advances in oncological management and radiosurgery.⁸⁵ The extent of epidural compression according to the spine oncology group’s six-point grading system (N), tumour radiosensitivity (O), mechanical stability of the spine as assessed by the SINS score (M), and the patient’s fitness for surgery (S) are domains to be considered. Surgery is indicated in the presence of mechanical instability, or high-grade epidural spinal cord compression (ESCC) resulting in neurological deficits. Separation surgery in high-grade ESCC is essential for optimal delivery of post-operative SBRT as will be elaborated upon below,⁸⁵ although cEBRT may suffice with radiosensitive tumours.⁸⁵ SRBT or cEBRT, as dictated by radiosensitivity, may be considered to provide definitive local treatment of spinal metastasis in the absence of significant neurological deficits, or when surgery cannot be tolerated.⁸⁶ SBRT guidelines have also been published from the International Stereotactic Radiosurgery Society (ISRS) recommending treatment for de novo spinal metastasis in the context of oligometastasis, radioresistant histology, and paraspinal soft tissue extension.⁸⁷ Contraindications include expected survival <3 months, >3 sites involved, mechanical instability, and spinal cord compression.

Separation Surgery

The working principle of separation surgery is to remove epidural tumour circumferentially from the spinal cord, thereby creating a safe window for the delivery of post-operative stereotactic radiosurgery.⁸⁸ Technically, this typically involves a posterior approach to the spine followed by a wide laminectomy, insertion of pedicle/lateral mass screws, and a fixation construct spanning a minimum of 2 levels above and below the site of compression.⁸⁹ A 2 mm margin is meticulously created between the thecal sac and surrounding tissues by removal of tumour tissues.⁹⁰ A caveat in the posterior approach which is favoured in over 80% of patients undergoing surgery for spinal metastasis³ is inadequate ventral decompression due to limited exposure and visualization. Over the thoracic and lumbar spine, access for ventral decompression may be facilitated by unilateral/bilateral facetectomy, pedicle removal, and ligation of non-essentially nerve roots. Intra-operative ultrasound has demonstrated utility in assessment of ventral decompression.⁹¹ The combination of separation surgery with percutaneous fixation techniques have been reported to reduce blood loss, inpatient stay, and complication rates.⁹²

Outcomes

A systemic review of over 1000 patients with metastatic spinal disease and treated by SBRT reported local control at 15 months to be 90%.⁹³ Even amongst radioresistant tumours such as sarcomas⁹⁴ and renal cell carcinomas,⁹⁵ local control at 1-year exceeded 80%. With the availability of effective systemic treatment, 1-year disease-free progression in patients with spinal metastasis has been reported to exceed 80% amongst a cohort of patients predominantly suffering from renal cell carcinoma.⁹⁶ Mechanically unstable spines and those with high grade cord compression and requiring upfront surgical decompression exhibited poorer rates of local control.²

In patients receiving surgical intervention followed by SBRT, local treatment failure at 1-year was demonstrable in only 19% of patients. On the contrary, a 1 -year local progression rate of 69.3% was reported in patients receiving surgery followed by cEBRT.⁹⁷ A two-week interval between surgery and radiotherapy is often recommended to allow time for wound healing, and this waiting period may be shortened following MIS techniques.⁹⁸ Failure to achieve gross tumour removal and to downstage epidural tumour compression limits radiation dosage and results in treatment failure,⁹⁹ emphasising the importance of surgeon understanding and execution in the principles of separation surgery as described above. In patients with lower grade epidural compression and mild neurological symptoms, SBRT has been demonstrated to be non-inferior to surgical decompression.¹⁰⁰

Outcomes with regards to pain control are similarly robust, with complete pain response achieved in 54% of patients receiving SBRT as compared to 23% in those receiving conventional radiotherapy.⁸⁷ Reduction in pain scores persist for at least 1-year in nearly 90% of patients.¹⁰¹ Reliance on narcotics was decreased, being utilized in 36% of patients at 6-months post-treatment as compared to 60% at baseline.¹⁰²

Re-irradiation of spinal metastases via SBRT has been deemed to be both safe and efficacious, therefore advocated by the ISRS.¹⁰³ In this context, rate of 1-year local control was 76%, and survival ranged from 10 – 22.5 months. Re-irradiation has also been described to provide pain relief and neurological improvement in 60% and 53% of patients respectively.^103,104 Nevertheless, re-evaluation by the spine surgeon is essential, specifically for evaluation of mechanical stability and high-grade epidural disease.

Complications

Radiation myelopathy represents a spectrum of disease occurring due to field effect upon the spinal cord, with an incidence of .4% upon review of 1400 patients.⁹³ Early delayed injury, or L’hermitte’s syndrome, causes parasthesia over the back and limbs upon neck movement. This usually presents 2-4 months after irradiation and is self-limiting. Late radiation myelopathy occurs on average 18 months after treatment and is diagnosed by exclusion. Clinical manifestations vary in severity from mild motor and sensory deficits to complete motor paralysis and is often irreversible. The spinal cord has the capacity for recovery after receiving occult radiation injury. Upon re-irradiation however, there is greater sensitivity to damage¹⁰⁵ and the incidence of radiation myelopathy rises to 1.2%.¹⁰³ There is some evidence that radiation myelopathy is steroid-responsive.¹⁰⁶

In addition to spinal cord radiotoxicity, other organs juxtaposed against metastatic tissues may be injured. An example is esophagitis, which is usually manifest within a few weeks of receiving SBRT to the cervical/thoracic region.¹⁰⁷ Management is symptomatic with analgesics and change to a fluid/soft diet.¹⁰⁸

Vertebral compression fractures (VCFs) subsequent to SBRT are not uncommon, with reported rates of approximately 20%,¹⁰⁹ and two-thirds occur within 4-months of treatment.¹¹⁰ Lower rates of vertebral fracture (5%) have been reported following conventional radiotherapy.¹¹¹ Higher epidural spinal compression grading, SINS scores, osteolytic volume and extent of vertebral body involvement have been identified as risk factors¹¹² and have been incorporated into risk scoring systems.¹¹³ Salvage procedures are required in more than 30% of patients suffering from SBRT-induced VCFs, with percutaneous cement augmentation being the most common treatment received in the absence of mechanical instability, compression of neural elements, and deformity.¹¹¹ Open surgery for VCFs is a major undertaking, with additional risks following SBRT as irradiated soft tissues are prone to non-healing and developing wound infections.

Conclusion

Advances in oncological management have vastly improved upon the prognosis of metastatic spinal disease. More patients are presenting as eligible surgical candidates, either towards a curative or palliative intent. The spine surgeon is a key member of the multidisciplinary team and should be cognizant of when to operate, and what the underlying surgical objectives are.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Graham Ka Hon Shea

Kenny Yat Hong Kwan

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Management of Metastatic Spinal Disease – A Practical Approach

Abstract

Study Design

Objective

Methods

Results

Conclusion

Keywords

Introduction

Epidemiology

Pathophysiology of Spinal Metastasis

Presentation of Metastatic Spinal Disease

Diagnostic Workup

Imaging

Surgical Biopsy

Clinical Decision-Making

Overall Prognosis

Disease Burden and Localization

Mechanical Instability

Neurological Compromise

Medical Management of Metastatic Spinal Disease

Oncological Treatment of the Primary Tumour

Prevention of Skeletally-Related Events (SREs)

Tumour Pain

Corticosteroid Therapy

Prevention of Venous Thromoboembolism

Surgical Options for Metastatic Spinal Disease

Curative Resection

Surgical Decompression and Fixation

Local Ablative Procedures and Vertebral Augmentation

Stereotactic Body Radiotherapy and Separation Surgery – How do They Fit in the Spine Surgeon’s Armamentarium

Principles of SBRT

Patient Selection

Separation Surgery

Outcomes

Complications

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

ORCID iDs

References