Management – spinal metastases

Handbook of Clinical Neurology, Vol. 149 (3rd series) Metastatic Disease of the Nervous System D. Schiff and M.J. Van den Bent, Editors https://doi.org/10.1016/B978-0-12-811161-1.00016-5 Copyright © 2018 Elsevier B.V. All rights reserved

Chapter 16

Management – spinal metastases 1

ANICK NATER1, ARJUN SAHGAL2, AND MICHAEL FEHLINGS1* Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada

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Department of Radiation Oncology, Sunnybrook Odette Health Sciences Centre, University of Toronto, Toronto, ON, Canada

Abstract Due to a worldwide increase of cancer incidence and a longer life expectancy of patients with metastatic cancer, a rise in the incidence of symptomatic vertebral metastases has been observed. Metastatic spinal disease is one of the most dreaded complications of cancer as it is not only associated with severe pain, but also with paralysis, sensory loss, sexual dysfunction, urinary and fecal incontinency when the neurologic elements are compressed. Rapid diagnosis and treatment have been shown to improve both the quality and length of remaining life. This chapter on vertebral metastases with epidural disease and intramedullary spinal metastases will be discussed in terms of epidemiology, pathophysiology, demographics, clinical presentation, diagnosis, and management. With respect to treatment options, our review will summarize the evolution of conventional palliative radiation to modern stereotactic body radiotherapy for spinal metastases and the surgical evolution from traditional open procedures to minimally invasive spine surgery. Lastly, we will review the most common clinical prediction and decision rules, framework and algorithms, and guidelines that have been developed to guide treatment decision making.

In accordance with the patient’s goals of care, the treatment of metastatic spinal disease (MSD) is to maintain or improve the quality of remaining life using palliative treatments. Although long-term survival has been reported in a few patients, especially with a solitary spinal metastasis (Sundaresan et al., 2002; Singletary et al., 2003; European School of Oncology MBC Task Force, 2007; Mesfin et al., 2015) and oligometastatic disease (Thibault et al., 2014), for the large proportion of patients survival is short. Treatments for MSD aim at short-term local disease control, alleviating pain, preventing or relieving spinal cord compression, preserving or restoring neurologic functions and spinal stability. Given that MSD is the expression of a systemic disease, its optimal management requires a multidisciplinary therapeutic approach involving medical and radiation oncologists, diagnostic and interventional radiologists, neurologists, surgeons, and palliative care pain control specialists.

With respect to treatment options, our review summarizes the evolution of conventional palliative radiation to modern stereotactic body radiation therapy (SBRT) for spinal metastases as well as the surgical evolution from traditional open procedures to minimally invasive spine surgery (MISS); the concept of separation surgery is also presented. Lastly, we introduce a few clinical prediction and decision rules, frameworks, or algorithms that have been developed to guide treatment decision making.1

STEREOTACTIC BODY RADIOTHERAPY Radiation-induced cell death is dependent on the biologic effective dose such that both a higher dose per fraction and total radiation dose potentiate more cell death. Given the limited ability of conventional external-beam radiation therapy (cEBRT) to deliver an effective dose to

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Abbreviations used in the chapter are listed at the end of the chapter before References section.

*Correspondence to: Michael G. Fehlings, MD, 399 Bathurst Street, 4W449, Toronto Western Hospital, Toronto, Ontario M5T2S8, Canada. Tel: +1-416-603-5072, E-mail: [email protected]

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a spinal target lesion while respecting safe tolerance thresholds of the surrounding normal tissues, such as the esophagus and the spinal cord, cEBRT is a locally palliative treatment option rather than a locally ablative option (Chan et al., 2014). Over the years, cEBRT has been shown to be associated with suboptimal pain and tumor control in the treatment of painful bone metastases, especially for relatively radioresistant tumors, such as nonsmall cell lung cancer, melanoma, renal cell carcinoma, and sarcoma, as well as tumors with paraspinal bulk (Mizumoto et al., 2011). A meta-analysis comparing lowdose single-fraction and multiple-fraction cEBRT revealed that, while both protocols provided partial pain relief in about two-thirds of patients, fewer than 1 out of 5 patients achieved complete pain relief. Furthermore, the retreatment rate was significantly higher for patients treated with low-dose single-fraction (20.4%) compared to those treated with higher-dose multiple-fraction (7.7%) (Chow et al., 2012). Ultimately cEBRT, whether single-fraction or multiple-fraction, is best suited for the patient with a limited life expectancy of 3–6 months. Before the advent of spine radiosurgery, also known as SBRT, only palliative practices with limited shortand longer-term benefits were available to patients with a greater life expectancy. The American College of Radiology and the American Society for Radiation Oncology defined SBRT as “an external beam radiation therapy method used to very precisely deliver a high dose of radiation to an extracranial target within the body, using either a single dose or a small number of fractions” (American College of Radiology (ACR), 2009). The extension of cranial stereotactic radiosurgery to the treatment of vertebral lesions (body targets) was challenging given the demands for precision of 1–2 mm and 1–2° in delivery, which could only be achieved using a rigid anchor frame such as the skull. Furthermore, treatment planning and delivery apparatus had to develop methods for highly collimated beams of radiation to conform to highly irregular targets and yield steep dose gradients to maximize dose at the interface of the spine and spinal cord. Figure 16.1 is an example of a typical spine SBRT dose distribution for a patient treated with 24 Gy in two fractions. Over the last two decades, advances in stereotactic computer-assisted navigation, image-guided techniques, development of robust noninvasive immobilization methods, and intensity-modulated radiation therapy have permitted the development of SBRT (Jabbari et al., 2016). The University of Toronto reported an evaluation of their system, and demonstrated the ability to localize the spinal target to within 1.2 mm and 0.9° with 95% confidence (Hyde et al., 2012). Different commercial SBRT systems are currently available for spine SBRT, each with unique image-guided mechanisms for position

Fig. 16.1. A typical spine stereotactic body radiotherapy dose distribution for a patient with the entire spinal segment involved with tumor requiring a “donut” distribution. The patient is treated with 24 Gy in two fractions. The dose distribution is intended to maximize high dose within the target and minimize the dose exposure to the surrounding normal tissues, but the area of maximal dose gradient is at the spinal cord interface. At the University of Toronto, we apply a 1.5-mm margin beyond the true spinal cord (yellow contour) to create a spinal cord planning risk volume (green color wash). The spinal cord is contoured based on magnetic resonance imaging fusion to the planning computed tomography.

verification and confirmation of dose as well as target treatment delivery (Swift, 2009; Chan et al., 2014). At present, most modern radiation delivery devices known as linear accelerations (linac) are able to perform spine SBRT. A detailed review of the clinical and technical issues surrounding spine SBRT has recently been reported by Jabbari et al. (2016) for the interested reader. Diverse treatment protocols have been reported with respect to spine SBRT dose fractionation for spinal metastasis with no epidural spinal cord compression, and at this time there is no optimal regimen with respect to efficacy. Common SBRT fractionation schemes include 24 Gy in one, two, or three fractions, 30 Gy in three to five fractions, and 25–40 Gy in five fractions. What we have learned is that choice of dose fractionation can influence the rates of vertebral compression fracture (VCF) postSBRT. VCF is the most common adverse event associated with spine SBRT, and when the dose per fraction is
20 Gy, a 40% rate of VCF is observed (Sahgal et al., 2013a). At the University of Toronto, the preferred treatment approach is 24 Gy in two fractions (i.e., two fractions of 12 Gy), and it is the SBRT fractionation schedule on the

MANAGEMENT – SPINAL METASTASES SBRT arm on the national phase III randomized controlled trial sponsored by the Canadian Clinical Trials Group (SC24 trial) comparing 20 Gy in five fractions of cEBRT to 24 Gy in two fractions of SBRT. At present, the evidence specific to spine SBRT is limited to single or small multicenter retrospective studies and a few prospective trials. However, the data suggest that SBRT is safe and efficient in achieving pain relief and local control for spinal metastases without epidural spinal cord compression, even in cases of radioresistant tumors such as renal cell tumors, sarcoma, and colon cancer (Hall et al., 2011; Bhatt et al., 2013; Chow et al., 2014; Harel and Zach, 2014; Thibault et al., 2015; De Bari et al., 2016). Based on a review of 15 studies comprising 1775 lesions in 1,388 patients treated with SBRT and with a mean follow-up of 15 months, 79% of patients achieved pain relief (partial or complete) and 90% local control (Hall et al., 2011). Although spine SBRT is more time consuming and costly than cEBRT, uncontrolled studies support that SBRT is superior to cEBRT for tumor and pain control for untreated, previously cEBRT-radiated, and surgically treated spinal metastasis (Hall et al., 2011; Bhatt et al., 2013; Chow et al., 2014; Harel and Zach, 2014; Thibault et al., 2015; De Bari et al., 2016). Caution is warranted in making conclusions as to superiority given the limitations of the quality of evidence and inability to directly compare outcomes between individual series due to heterogeneity in both patient and tumor baseline characteristics, variation in the total dose and dose/fraction delivered, and lack of standardized outcome measures for both pain and tumor response. What is needed are randomized controlled trials to prove the superiority of SBRT, and they are ongoing globally.

Points of caution with spine SBRT Radiation-induced spinal cord injury, VCF, and local recurrence are the major complications related to spine SBRT. Given the evidence-based spinal cord dose limits by Sahgal et al. (2013b) for both patients with and without prior radiation exposure, radiation-induced myelopathy has again become a rare event despite the high doses associated with SBRT. However, VCF has arisen as the most common and serious complication of spine SBRT, ranging from 10% to 40%, and mostly related to highdose single-fraction SBRT as opposed to fractionated SBRT (Sahgal et al., 2013a). Although late cases of VCF have been reported secondary to necrosis of the bone tissue, it is often perceived as an acute or subacute complication given that approximately 60% of events occur within the first 4–6 months following spine SBRT. The pathophysiology in this time frame is related to necrosis and likely an intense inflammatory reaction within the vertebral body.

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VCF is clinically significant as patients may suffer from persistent or worsening axial or radicular pain as well as neurologic deficits. Typically, a third of patients developing VCF require some intervention, which is usually a minimally invasive procedure such as percutaneous cement augmentation. The use of prophylactic surgical stabilization is controversial. Based on risk factor analyses from a large cohort of patients from the MD Anderson Cancer Center, Cleveland Clinic, and University of Toronto, in patients with pre-existing VCF and >50% height loss, significant lytic destruction, spinal deformity, and an intent to treat with
20 Gy per fraction, prophylactic stabilization may be considered (Chan et al., 2014; Chang et al., 2016; Jabbari et al., 2016). Prospective trials are needed to determine evidence-based patient selection before this practice can be considered standard of care given the potential implications for patients of enduring a surgical procedure. Among spinal segments with local progression, the rate of epidural disease progression is 67% (range, 38–96%), making it the most common pattern of failure observed specific to spine SBRT. This phenomenon may be an issue of dose as the spinal cord is exposed to a lower dose than that prescribed to the tumor in order to respect spinal cord tolerance and/or bad biology, as frequently it is pre-existing epidural disease that is progressive. The attention to epidural grade has been shown to be an important factor in terms of selecting patients for SBRT and it has been shown that downgrading epidural disease, for instance from a Bilsky grade 2 to a grade 1b, results in better outcomes for patients following SBRT (Al-Omair et al., 2013). This phenomenon has also resulted in innovative new methods to deal with epidural disease such as separation surgery, which entails a circumferential resection of the spinal tumor starting from normal dural planes to achieve spinal decompression with a tumor-free margin of 2–3 mm around the dural sac (Laufer et al., 2013a). Separation surgery can be achieved as an outpatient day intervention either via a minimally invasive spinal surgery procedure (Massicotte et al., 2012) or ablation with magnetic resonance imaging (MRI)-guided laser interstitial thermotherapy (Chan et al., 2014; Tatsui et al., 2015; Chang et al., 2016; Jabbari et al., 2016). Response determination following spine SBRT has been identified as a significant challenge and area of research. The community has come to realize that signal changes on MRI post-SBRT within the bone tissue are difficult to interpret, and osseous pseudoprogression is increasingly recognized as a potential confounder in response determination (Amini et al., 2016). The Spine Response Assessment in Neuro-oncology group highlighted that signal changes on T1- and T2-weighted MRI, with or without contrast enhancement, can be

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observed after spine SBRT and do not necessarily imply tumor progression or response (Thibault et al., 2015; Bahig et al., 2016). This group has made several recommendations with respect to practice standardization and response definitions to help guide research and clinical trial methods until we have more data. In conclusion, spine SBRT has shown promising results for patients with spinal metastases. The indications of spine SBRT will continue to evolve as clinical data increase. At present, it is currently used for: (1) the initial treatment of spinal metastasis for patients with oligometastatic disease; (2) the treatment of residual tumor after surgical resection; and (3) tumor progression or recurrence after surgery or cEBRT. Contraindications include poor performance status (Eastern Cooperative Oncology Group (ECOG) 3–4 or Karnofsky Performance Status (KPS) <60%); widely metastatic and/or rapidly progressing metastatic disease with limited life expectancy (under 3 months); >3 contiguous spinal levels involved or diffuse spinal disease, patients with spinal instability (Spinal Instability Neoplastic Score (SINS) 13–18), high-grade epidural disease (Bilsky grade 3), and/or neurologic deficit due to epidural compression by bone or tumor, and prior cEBRT or SBRT within 3 months of the intended SBRT treatment. A complete list of indications – clinical, radiographic, and technical – has been recently summarized by Jabbari et al. (2016).

SURGERY Open surgery cEBRT became the mainstay treatment for MSD after a small randomized clinical trial (Young et al., 1980) suggested that cEBRT alone was as efficacious as laminectomy followed by cEBRT in relieving pain and improving both ambulation and sphincter control in patients with metastatic epidural spinal cord compression (MESCC). In addition, one prospective study reported that laminectomy was associated with a higher incidence of major neurologic decline and spinal instability (Findlay, 1987). In fact, 80% of MSD involves the vertebral bodies (White et al., 2006), which absorb 80–90% of the axial load bearing (Ecker et al., 2005), and neoplastic tissue has minimal weight-bearing properties promoting anterior column collapse (Jacobs and Perrin, 2001), i.e., VCF. Thus, in most patients with MSD, not only does a simple laminectomy not appropriately address the pathology, but it also weakens the posterior column, increasing the risk of spinal instability, especially in the context of vertebral collapse, with subsequent kyphosis, worsening pain, and further compromise of neurologic elements as a result. A better understanding of

spine biomechanics and the sophistication of surgical approaches, such as posterolateral and anterior exposures to achieve circumferential decompression as well as the improvement of spinal stabilization techniques and devices, promoted the efficacy of surgery in the management of patients with MSD. Patchell et al. (2005) conducted a seminal randomized clinical trial comparing surgical circumferential spinal decompression followed by cEBRT (30 Gy in 10 fractions) to a cEBRT regimen alone in patients suffering from a symptomatic MESCC lesion. They defined MESCC as an epidural mass originating from a single spinal segment and displacing the spinal cord from its normal position in the spinal canal. This study was stopped at the time of a planned interim analysis as patients in the surgical arm showed a definite advantage over those in the cEBRT-only group with regard to the primary outcome of ambulatory status, with higher ambulatory rates (84% vs. 57%), recovery (63% vs. 19%) and duration (median 122 vs. 13 days). In addition, surgically treated patients required less opioid analgesics and corticosteroids, and tended to survive longer. Lastly, surgery did not increase the hospital stay and the 30-day morbidity was worse in the cEBRT only group. However, this study had several limitations. First, the eligibility criteria were strict and question the generalizability of the results. Admissibility to the study included: adult patients with an acceptable general medical status to tolerate surgery, a life expectancy of at least 3 months, and presentation with a single MESCC lesion creating pain; the presence of neurologic dysfunction was not mandatory. Importantly, patients with an MESCC from a radiosensitive histology, compression of the cauda equina and/or spinal roots, and with complete paraplegia for >48 hours prior to study enrollment were excluded. Other limitations included the lack of technical surgical standardization, and a limited sample with 101 patients recruited over 10 years. Lastly, there may be an inherent patient selection bias favoring surgery given that the patient selection process did not account for the fact that patients with mechanical pain/instability would not benefit from cEBRT. Nevertheless, two meta-analyses have concluded that decompressive surgery followed by cEBRT is associated with better ambulatory status than cEBRT alone (Klimo et al., 2005; Lee et al., 2014). To add to this evidence, the AOSpine North America Clinical Research Network undertook a prospective, multicenter study which showed the complementary value of decompression/ reconstructive surgery to radiotherapy (RT) in patients with spinal oligometastatic disease (Fehlings et al., 2016). However, an economic systematic review reported that, although surgery and cEBRT is more

MANAGEMENT – SPINAL METASTASES effective for these patients, it is much costlier than cEBRT alone (Fehlings et al., 2014). Given that MSD is the expression of a systemic disease, its optimal management requires a multidisciplinary therapeutic approach involving medical and radiation oncologists, diagnostic and interventional radiologists, neurologists, surgeons, and palliative care pain control specialists, and in the light of the latter evidence, patients with a symptomatic single-level MESCC should be offered a surgical consultation. In addition, although the majority of patients with MSD have limited survival (Fehlings et al., 2016), among the 1266 surgically treated patients enrolled in the Global Spine Tumour Study Group registry with data suitable for analysis, 16.3% died within 3 months of surgery while 26.3% survived for more than 2 years (Verlaan et al., 2016). Consequently, considerable judgment is required to select the optimal surgical strategy to avoid undertreating patients who would benefit from maximal decompression, reconstruction, and stabilization given a good general status and longer potential survival. Furthermore it is important to avoid overtreating patients for whom a surgical intervention might result in shortening their life expectancy.

Surgical techniques There are various types of direct decompressive procedures in spinal oncology that range from intratumoral curettage to wide-margin en bloc vertebrectomy. It should be emphasized that in the context of MSD true en bloc procedures are virtually impossible as one cannot resect the entire dura to achieve a R0 margin, i.e., no neoplastic cells at the margin of the en bloc specimen on pathologic evaluation. With respect to approach, given that the majority of spinal metastasis involve the vertebral body, tumor resection and spinal reconstruction are in theory best achieved via anterior surgical approaches. However, in practice, apart from the subaxial cervical spine, anterior approaches are typically quite time consuming and technically challenging. To access the thoracic or lumbar column anteriorly, surgeons have to avoid injuring and work around visceral organs, nerves, and blood vessels. Fortunately, transpedicular, costotransversectomy and lateral extracavitary approaches (Fig. 16.2) have been developed, allowing a safe access to the anterior column from a posterior incision (Eleraky et al., 2010; Kaloostian et al., 2014b) and this dramatically facilitates more aggressive surgical procedures aimed at tumor debulking. Given the width of the spinal canal at the craniocervical junction (occiput–C2), spinal stability is a more common issue than spinal cord compression. Transnasal, transcervical, or transoral approaches are seldom performed, in

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Fig. 16.2. (A) Lateral extracavitary, (B) transpedicular, and (C) costotransversectomy approaches to access the vertebral body from a posterior incision. The dashed lines represent the amount of rib removal typically involved in each approach.

contrast to posterior decompression and stabilization. In the subaxial cervical spine (C3–C6), anterior cervical decompression with corpectomy and reconstruction using a cage graft is appropriate in most cases (Fig. 16.3), while in the cervicothoracic junction (C7–T1), either an anterior or posterior approach can be used. In both the subaxial and cervicothoracic junction, an anterior approach can be supplemented by lateral mass screws/posterolateral instrumentation and fusion for greater stabilization, such as for multilevel disease, metastasis involving both the anterior and posterior columns, and poor bone quality (Fehlings et al., 2009). The presence of the great vessels complicates anterior approaches for upper anterior thoracic metastases (T2–T5), thus posterior approaches are favored. As opposed to T1–T2 nerve roots innervating the upper extremities, the T3–T12 nerve roots can be sacrificed without significant clinical consequences. In the midthoracic to lumbar spine, anterior, posterior, or combined approaches can be employed according to the clinical situation as well as surgeon and patient preferences (Polly et al., 2009; Eleraky et al., 2010; Kaloostian et al., 2014b). Although recent studies showed that surgery for sacral metastasis is associated with rapid pain relief, improved constipation, quality of life, and acceptable morbidity (Feiz-Erfan et al., 2012; Du et al., 2016), these lesions are generally not surgically treated. Given the dimension of the spinal canal at the sacral level, neurologic deficits are rare. Moreover, not only is extensive bone destruction required to create sacral instability, but when it occurs, it is subsequently usually difficult to stabilize the lumbosacral junction. When surgery is performed, it is most often via a posterior approach (Nader et al., 2004). Of note, spinal stabilization is often advisable for MSD involving a junctional region, in particular if anterior and posterior element destruction is present. Although RT and surgery are both effective in treating MESCC caused by soft-tissue tumor, surgical

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Fig. 16.3. This 51-year-old man presented with neck pain which worsened and started radiating to his arms. He had a cervical X-ray which was suspicious for a pathologic process at C4. Upon further investigation, the patient was diagnosed with plurimetastatic nonsmall cell lung carcinoma. He received five fractions of conventional external-beam radiotherapy (cEBRT) to his C4 lesion. Unfortunately, within 1 month posttreatment, he developed profound right shoulder weakness and worsening pain. With a mobile spinal location (2 points), mechanical pain (3 points), lytic bone lesion (2 points), normal radiographic spinal alignment (0 points), less than 50% vertebral body collapse (2 points), and bilateral posterolateral involvement of spinal elements (3 points), the Spinal Instability Neoplastic Score was 12 points. Surgery was thought to be warranted to stabilize his spine and relieve the pressure on the spinal cord and right C5 nerve. He underwent an urgent anterior cervical decompression with a C4 vertebrectomy, reconstruction, and stabilization. Postoperatively, his pain and motor strength were significantly improved; he was left with a mild right C5 residual palsy. The initial nonenhanced sagittal cervical T2-weighted (A) and T1-weighted (B) magnetic resonance imaging (MRI) showing metastatic invasion of the C4 vertebral body with extension into the epidural space and encroachment of the spinal cord. Imaging obtained at the onset of neurologic decline after cEBRT treatment revealed an interval progression of bony metastatic disease with C4 pathologic fracture and retropulsion of osseous fragment into the anterior spinal canal and compression of the spinal cord and right C5 nerve: nonenhanced sagittal T2-weighted (C) and T1-weighted (D) MRI with its corresponding axial image (E), and sagittal plane computed tomography scan (F). Follow-up cervical anteroposterior (G) and lateral (H) radiographs showing an anterior internal reconstruction with titanium mesh cage and anterior cervical plate fixation.

decompression, usually with stabilization, followed by RT is the favored treatment for a single symptomatic epidural lesion. Surgery is also typically preferred when MESCC is secondary to bony compression, kyphotic

deformity, or radioresistant tumor, or in the event of impeding or frank spinal instability/deformity which could lead to pain and compression of neurologic elements. Other indications for surgery include progressive

MANAGEMENT – SPINAL METASTASES neurologic decline before or during RT treatment, or cases where the maximal spinal cord radiation dose tolerance has been reached (Prasad and Schiff, 2005; Bartels et al., 2008). Several studies reported that surgical intervention enhances quality of life by providing immediate and prolonged pain relief, as well as improved functional and neurologic status (Wai et al., 2003; Patchell et al., 2005; Falicov et al., 2006; Jansson and Bauer, 2006; Ibrahim et al., 2008; Fujibayashi et al., 2010; Pointillart et al., 2011; Quan et al., 2011; Fehlings et al., 2016). However, among all skeletal-related events in cancer patients, MESCC treated with surgery is the most costly (Jayasekera et al., 2014). In addition, the surgical morbidity and mortality rates need to be considered as the impact on the patient in the short term can be significant. A systematic literature review reported a 30-day postoperative mortality rate of 5% (0–22%) and an overall complication rate of 29% (5–65%) (Kim et al., 2012). Considering the time expected for most beneficial effects to be realized by the patient secondary to recovery from the surgical intervention and potential complications, surgery followed by adjuvant RT is often offered to patients with a life expectancy of at least 3 months, and RT alone if less than 3 months despite a surgical indication (Bartels et al., 2008; Choi et al., 2010; Eleraky et al., 2010; Laufer et al., 2012; Loblaw et al., 2012; Ribas and Schiff, 2012; Dea and Fisher, 2014; Kaloostian et al., 2014a; Verlaan et al., 2016). However, there is no consensus regarding a life expectancy threshold to suggest surgical over conservative treatment. It should be emphasized that physicians tend to inaccurately estimate life expectancy in patients with advanced cancer. In their systematic literature review, Cheon et al. (2016) reported that clinicians overestimated and underestimated survival in twelve and five studies, respectively. The authors concluded that clinical prediction tools for survival should be further examined. Unfortunately, a systematic literature review revealed that the quality of evidence for preoperative predictors of survival in patients with a symptomatic MESCC lesion who were surgically treated was, at best, low (Nater et al., 2017). However, a study published after the timeframe considered by the latter systematic review used the data provided by the Global Spine Tumour Study Group, a prospective, observational, multicenter, longitudinal cohort study, in which all surgical patients with MSD were given a life expectancy of at least 3 months by their treating oncologist. While lower KPS and higher age were significant preoperative predictors for the 173 out of 1060 patients (16.3%) who died within 3 months after surgery, the 221 surgical patients who survived for longer than 2 years after surgery had a more favorable primary tumor histology, such as

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myeloma, and had a lower number of affected spinal levels surgically treated compared to the 661 patients who died within 2 years. With the perpetual striving to improve physicians’ ability to select adequate surgical candidates comes a discussion of novel surgical techniques aimed at reducing surgical morbidity while still offering the benefits of surgery.

MINIMALLY INVASIVE SPINE SURGERY McAfee et al. (2011) stated that the key principles of MISS are the reduction of iatrogenic muscle crush injury by using tubular-type table-mounted retractors, and application of soft-tissue dilation techniques rather than selfretaining retractors and stripping techniques. Although MISS is still not well defined relatively to mini-open surgery, it often involves small incisions, usage of natural anatomic planes, preservation of posterior motion segments and paraspinal muscles, which minimize the risk of muscle atrophy and chronic pain. In addition, it is associated with less operative blood loss and reduced need for postoperative analgesics, thereby promoting shorter hospital stay, faster recovery, and earlier return to normal life activities (McAfee et al., 2011; Smith and Fessler, 2012; Banczerowski et al., 2015). In their recent systematic review, Zuckerman et al. (2016) concluded that MISS is safe and effective in achieving decompression and stabilization in MSD patients, and clinical benefits are associated with both percutaneous fixation with pedicle screw cement augmentation in patients with mechanical instability and mini-open, tubular retractors or thoracoscopy/ endoscopy in MESCC patients.

Percutaneous vertebral cement augmentation procedures Percutaneous vertebral cement augmentation procedures are gaining popularity in the treatment of vertebral metastasis associated with mechanical pain. Vertebroplasty, kyphoplasty, and skyphoplasty are licensed for clinical use (Kassamali et al., 2011). Vertebroplasty was first introduced in the late 1980s by Pierre Galibert, a French neurosurgeon, to achieve vertebral stabilization of a painful cervical hemangioma. The percutaneous approach involving bone needle cannulas was then developed by Herve Deramond, a French interventional radiologist. Galibert and Deramond also noted significant pain relief associated with pouring cement into the diseased vertebral body (Galibert et al., 1987). Pain relief is thought to result from both the exothermic reaction following the injection of cement within the diseased vertebral body, which is believed to damage surrounding nerve endings, and the mechanical

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stabilization offered by the compression-resistant cement (Stephenson et al., 2016). Under local anesthetic, sedation, and fluoroscopic image guidance, vertebroplasty implies the direct injection of quick-setting bone cement, typically polymethylmethacrylate (PMMA), under high pressure until the anterior two-thirds of the vertebral body is evenly filled. Kyphopasty and skyphoplasty are conducted under general anesthetic and provide the additional potential benefit of restoring vertebral body height. Both techniques involve creating a cavity by deploying an inflatable balloon (kyphoplasty) or a stiff plastic tube, which is crushed into a “popcorn-like” shape (skyphoplasty) into the vertebral body prior to the instillation of cement. In contrast to kyphoplasty, since skyphoplasty generates more pressure and allows more control over the direction of this pressure, it needs only one injection site (Kassamali et al., 2011). The Cancer Patient Fracture Evaluation (Berenson et al., 2011), a randomized clinical trial that involved 22 international centers, is the only comparative study assessing painful VCF specifically in patients with cancer. The use of analgesics, bed rest, bracing, physiotherapy, rehabilitation programs, walking aids, radiation treatment, antitumor therapy, calcium, vitamin D supplements, antiresorptive or anabolic agents was at the discretion of the treating physicians. Seventy patients with painful metastatic VCF underwent kyphoplasty in addition to conservative treatment while 64 did not. Posttreatment, only kyphoplasty patients showed significant improvement in functional status and quality of life as well as a decrease in analgesic use compared to pretreatment data. All other evidence related to vertebroplasty and kyphoplasty comes from studies involving patients with painful osteoporotic VCFs. Three recent meta-analyses comparing vertebroplasty and kyphoplasty for painful osteoporotic VCFs reported a lower cement leakage with kyphoplasty than vertebroplasty (Papanastassiou et al., 2012; Chang et al., 2015; Wang et al., 2015). However, although both vertbroplasty and kyphoplasty showed superior results in unblinded trials compared to optimal medical pain management treatments, there is no evidence that either procedure is superior to operative placebo, i.e., local anesthesia and insertion of a needle cannula without instillation of cement (Stevenson et al., 2014). Therefore, the cost-effectiveness of vertebroplasty and kyphoplasty has still not been demonstrated. Of note, kyphoplasty is 5–10 times more costly than vertebroplasty (Kassamali et al., 2011). Because they are associated with less soft-tissue trauma, blood loss, and anesthetic use, percutaneous vertebral augmentation procedures have lower potential morbidity and mortality than open spinal surgery. These

techniques are associated with 10% overall risk and <3% risk of major symptomatic complications. The most dreaded complication is related to cement leakage into the paravertebral venous plexus, the epidural space, or neural foramina, leading to pulmonary embolism or compression of neurologic elements, respectively. Despite cement extravasation occurring in up to 41% of vertebroplasty interventions, it is rarely clinically significant (Kassamali et al., 2011). However, the risk of complications such as cement or even tumor tissue extravasation is of greater concern in patients with MSD, primarily due to the fear of potentially causing or aggravating neurologic deficit. Evidence of destruction of the posterior cortical wall of the vertebral body without neurologic symptoms resulting from direct bony compression or paraspinal/epidural tumor extension is a relative contraindication to percutaneous vertebral cement augmentation procedures, while neurologic deficit resulting from MESCC is an absolute contraindication (Kassamali et al., 2011; Stephenson et al., 2016). However, a few small case series supported that vertebroplasty was safe and efficacious in achieving structural reinforcement and analgesia in patients with epidural tumor extension, with or without neurologic deficits (Shimony et al., 2004; Saliou et al., 2010; Sun et al., 2014).

Ablative procedures Ablative procedures have only been investigated in a few small case series, and there is a paucity of evidence regarding their safety and efficacy with regard to MSD with epidural extension.

Radiofrequency ablation Radiofrequency ablation of spinal metastasis can be performed using a similar setting as vertebroplasty; it is performed under local anesthesia and fluoroscopic guidance. A partially insulated electrode is inserted into the cannula; the ions emitted by the electrode connected to a radiofrequency generator are converted to heat (60–100°C/140–212°F), leading to protein denaturation and local cell death (Kassamali et al., 2011; Stephenson et al., 2016). Since radiofrequency ablation decreases vertebral tumor volume and significantly reduces pain as well as opioid usage (Goetz et al., 2004; Thanos et al., 2008), but does not prevent vertebral fracture or kyphosis, it was used in combination with vertebroplasty (Orgera et al., 2014), even patients with posterior wall defect (van der Linden et al., 2007), radiofrequency ablation (Zheng et al., 2014), and filling of the cavity with PMMA (Munk et al., 2009), and was reported safe and effective with less cement leakage than vertebroplasty and kyphoplasty.

MANAGEMENT – SPINAL METASTASES

Plasma-mediated radiofrequency ablation (coblation) In contrast to radiofrequency ablation, in plasmamediated radiofrequency ablation (coblation), the partially insulated electrode inserted into the cannula emits ions that cause the electric excitation of the plasma into a high-energy state that leads to the dissociation of molecular bonds under lower heat (40–70°C/104–158°F), creating a cavity within the tumor without violating the integrity of the adjacent tissue. PMMA is then used to fill the cavity cautiously along the path of least resistance toward the anterior portion of the vertebral body and away from the posterior wall, minimizing the risk of cement leakage into the spinal canal. Given that the risk of complications such as cement or tumor extravasation, and subsequent compromise of neurologic functions, is greater in patients with a defect in the posterior wall of the vertebral body, paraspinal or epidural extension, these patients are considered at higher risk for vertebroplasty or kyphoplasty. Coblation combined with cementoplasty provides these patients with an alternative percutaneous vertebral augmentation option while minimizing the risk associated with cement leakage and thermal injury to surrounding structures. The very limited evidence available to date suggests that coblation is safe and effective in reducing pain (Stephenson et al., 2016).

SEPARATION SURGERY Separation surgery refers to providing sufficient surgical circumferential decompression of the spinal cord to create at least 1–2 mm of space between the spinal cord and disease to optimize the SBRT dose distribution. Separation surgery is typically used in patients with high-grade MESCC (i.e., Bilsky grade 2 and 3), previously radiated or not, pathologic fracture, or mechanical instability. Although circumferential decompression of the spinal cord tends to be most often achieved using MISS methods, conventional open surgeries can also be used in separation surgery (Jabbari et al., 2016; Zuckerman et al., 2016). The largest retrospective series involved 186 MESCC patients treated with separation surgery, and postoperative radiation dose was the only factor significantly associated with local tumor progression: 1-year local progression was observed in 4% and 22% for high- and low-dose hypofractionated SBRT, respectively (Laufer et al., 2013a). Al-Omair et al. (2013) reported a therapeutic benefit with maximal epidural disease resection prior to SBRT. Local control rates were significantly better in patients with Bilsky grade 2 or 3, who downgraded to a grade 0 or 1 as opposed to a grade 2.

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THERAPEUTIC DECISION MAKING Given the frailty and hence the challenge of determining an accurate prognosis, therapeutic decision making in patients with MSD is complex. Treatment regimens vary widely according to availability of treatment modalities, geographic regions, medical costs, and patients’ and surgeons’ beliefs. Although there is no consensus or standardized approach to the management of MSD, prognostic tools, such as clinical prediction rules (Harrington, 1986; Bauer and Wedin, 1995; Sioutos et al., 1995; Katagiri et al., 2005; van der Linden et al., 2005; Bartels et al., 2007; Rades et al., 2008, 2010, 2013; Balain et al., 2013; Bollen et al., 2014; Ghori et al., 2015) and clinical decision rules (Tomita et al., 2001; Tokuhashi et al., 2005; Leithner et al., 2008), clinical framework (Paton et al., 2011; Laufer et al., 2013b), and clinical guidelines (NICE, 2008; Lutz et al., 2011) have been elaborated to assist physicians. Of note, while both clinical prediction rules and clinical decision rules provide probabilities, clinical prediction rules are assistive in nature and thus do not necessarily recommend decisions, whereas clinical decision rules are directive; they propose a specific management strategy based on the predicted probability values computed by the prognostic rule (Reilly and Evans, 2006). For instance, the revised Tokuhashi, Tomita, and modified Bauer score are clinical decision rules (Fig. 16.4), while the OSRI and 1-year survival prognostic score by Ghori et al. (2015) are clinical prediction rules (Fig. 16.5). A recent survey conducted among worldwide experts in the treatment of MESCC revealed that 22.2% did not use any scoring system or algorithm in their clinical practice. Among respondents who reported using a specific system, the revised Tokuhashi, Tomita, Neurologic, Oncologic, Mechanical instability, and Systemic (NOMS), OSRI, and SINS were the most cited ones (Nater et al., 2016). The revised Tokuhashi is a 15-point score that consists of six predictors (site of primary tumor, KPS, number of vertebral metastases, number of extraspinal bony metastases, metastases to major internal organs, and motor deficit). A score of 0–8 points estimates less than 6-month survival and suggests conservative or palliative surgery; a score of 9–11 points estimates 6–12-month survival and suggests palliative or excisional surgery could be considered for patients with a single spinal metastasis with no metastases to any major internal organs; while a score of 12–15 points estimates survival greater than 12 months and suggests excisional surgery (Tokuhashi et al., 2005). The Tomita score is based on three predictors (primary tumor growth rate, visceral metastasis, and osseous metastasis). A wide or marginal excision is suggested for a score of 2–3 points; marginal or interlesional

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revised Tokuhashi scoring system

Prognostic Factors Primary tumor site Slow growth (e.g. breast, thyroid, prostate) Moderate growth (e.g. kidney and uterus) Rapid growth (e.g. lung, stomach, colon, unknown primary) Visceral metastases None Treatable Untreatable Bone metastases, including spine Solitary or isolated Multiple

2 3 Long-term local control Wide or Marginal excision

Total score 4 5 6 7 Middle-term Short-term local control palliation Marginal or interlesional excision

Palliative surgery

Point

Prognostic Factors Point Primary tumor site Lung, Osteosarcoma, stomach, bladder, etc. 0 Liver, Gallbladder, Unidentified 1 Others 2 Kidney, Uterus 3 Rectum 4 Thyroid, Breast, Prostate, Carcinoid tumor 5 Number of vertebral body metastases 0 ≥3 1 2 2 1 Number of extraspinal bone metastases 0 ≥3 1 1-2 0 2 Karnofsky performance status Poor (10 – 40%) 0 1 Moderate (50 – 70%) Good (80 – 100%) 2 Metastasis to major internal organs

1 2 4

0 2 4 1 2

8 9 10 Terminal care Supportive care

Unremovable Removable None Palsy

A

Complete (Frankel A, B) Incomplete (Frankel B, C, D) None (Frankel E)

modified Bauer scoring system Prognostic Factors No visceral metastasis Primary tumor site is NOT lung Primary tumor is breast, kidney, lymphoma or MM Presence of one solitary bone metastasis

0–1 Supportive care No surgery

B

Total Score 2 Short term palliation Dorsal surgery

Point 1 1 1 1

3–4 Middle term local control Ventral-Dorsal surgery

0 1 2 0 1 2

Total Score (predicted survival) 0–8 9 – 11 12 – 15 (< 6 months) (6-12 months) (> 12 months) - Conservative - Palliative - Excisional treatment surgery surgery - Palliative - Excisional surgery* surgery** Conservative Treatment - Radiation - Chemotherapy - Hormonotherapy - Analgesia

Palliative Surgery - Posterior decompression and stabilization - Posterior stabilization - Laminectomy - Palliative anterior curettage and stabilization

Excisional Surgery - Anterior curettage and stabilization - Combined curettage and stabilization - En bloc resection and stabilization

C Fig. 16.4. Examples of clinical decision rules. (A) Tomita scoring system. (Modified from Tomita K, Kawahara N, Kobayashi T, et al. (2001) Surgical strategy for spinal metastases. Spine (Phila Pa 1976) 26: 298–306.) (B) Modified Bauer scoring system. MM, multiple myeloma. (Modified from Leithner A, Radl R, Gruber G, et al. (2008) Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur Spine J 17: 1488–1495.) (C) Revised Tokuhashi scoring system. *Palliative surgery is not considered in patients with poor general condition, complete paralysis 2–3 days after the onset of motor deficits, little interest in living or significant response to oral analgesics or radiotherapy. **Excisional surgery is only considered in patients with a single spine lesion and no metastasis to any major internal organ. (Modified from Tokuhashi Y, Matsuzaki H, Oda H, et al. (2005) A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine (Phila Pa 1976) 30: 2186–2191.)

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Oswestry Spine Risk Index (OSRI) Prognostic Factors Points Primary tumor pathology (PTP) Slow Breast, thyroid, prostate, myeloma, haemangioma, endothelioma, 1 non-Hodgkin’s lymphoma Moderate Kidney, uterus, tonsils, epipharynx, synovial cell sarcoma, 2 metastatic thymoma Rapid Stomach, colon, liver, melanoma, teratoma, pancreas, rectum, 4 unknown origin Very rapid Lung 5 General condition (GC - based on Karnofsky performance status (KPS)) Good KPS 80 – 100% 0 Moderate KPS 50 – 70% 1 Poor KPS 10 – 40% 2

OSRI score = PTP + (2 – GC)

A

OSRI score Prediction of median survival 85th centile of survival (Risk index) time in months (95% CI) time in months 1 23 (12 – 36) 69 2–3 6 (4 – 9) 30 4 –5 4 (3 – 5) 12 6 2 (1 – 3) 6 7 1 (1 - 2) 2 CI: confidence interval

Ghori scoring system Predictive score (% survival at 1-year)

Characteristics of predictive score

- Low modified Bauer score - Impaired ambulatory status - Preoperative albumin < 3.5 g/dL - Low modified Bauer score 1 - Intact ambulatory status (34.9%) - Low modified Bauer score - Preoperative albumin ≥ 3.5 g/dL - High modified Bauer score 2 - Intact ambulatory status (46.2%) - Preoperative albumin ≥ 3.5 g/dL - High modified Bauer score 3 - Intact ambulatory status (68.3%) - High modified Bauer score - Preoperative albumin ≥ 3.5 g/dL High modified Bauer score = modified Bauer score 3 or 4 Low modified Bauer score = modified Bauer score ≤ 2 0 (18.5%)

B

Fig. 16.5. Examples of clinical prediction rules. (A) Oswestry Spine Risk Index (OSRI). (Modified from Balain B, Jaiswal A, Trivedi JM, et al. (2013) The Oswestry Risk Index: an aid in the treatment of metastatic disease of the spine. Bone Joint J 95-B: 210–216.) (B) Ghori scoring system. (Modified from Ghori AK, Leonard DA, Schoenfeld AJ, et al. (2015) Modeling 1-year survival after surgery on the metastatic spie. Spine J 15: 2345–2350.)

excision for a score of 4–5 points; palliative surgery for a score of 6–7 points; and supportive care for a score of 8–10 points (Tomita et al., 2001). Although these clinical decision rules recommend treatment options, they are not well defined. The NOMS is a four-item therapeutic algorithm for MSD that was developed at the Memorial SloanKettering Cancer Center in New York, United States. The treatment decision depends on: (1) the neurologic, which is divided as Bilsky grade 0–1 (Fig. 16.6) with negative clinical evaluation of myelopathy and/or functional radiculopathy and Bilsky grade 2–3 with or without neurologic deficits; (2) the radiosensitivity of the

primary tumor dictates the oncologic component; (3) the spinal mechanical stability is assessed using the SINS (Figs 16.3 and 16.7); and (4) the systemic assessment implies determining whether a patient is likely to tolerate a surgical intervention. Overall, spinal instability generally mandates stabilization, which may be limited to percutaneous pedicles, screws, instrumentation, and/or vertebral cement augmentation, while radiosensitivity influences the use of SBRT or salvage EBRT as primary or adjuvant treatment following stabilization (Laufer et al., 2013b). OSRI was developed using the most predictive factors from the revised Tokuhashi, Tomita, and modified Bauer

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Fig. 16.6. Schematic of the 6-point Bilsky grading system of epidural spinal cord compression at a thoracic vertebra (Bilsky et al., 2010). (A) (1) epidural space; (2) spinal cord; (3) cerebrospinal fluid (CSF); (4) dural sac. (B) Bilsky grading system: grade 0: osseous involvement only; grade 1a: invasion of the epidural space without deformation of the dural sac; grade 1b: deformation of the dural sac without abutment of the spinal cord, i.e., there is still a rim of CSF visible around the spinal cord; grade 1c: deformation of the dural, spinal cord abutment without spinal cord compression; grade 2: spinal cord compression but with some CSF still visible; grade 3: spinal cord compression without CSF identifiable around the spinal cord. (Modified from Bilsky MH, Laufer I, Fourney DR, et al. (2010) Reliability analysis of the epidural spinal cord compression scale. J Neurosurg Spine 13: 324–328.)

Spinal Instability Neoplastic Scale (SINS) Description Points Junctional (Occ-C2, C7-T2, T11-L1, L5-S1) 3 2 Mobile (C3-6, L2-4) Semi-rigid (T3-10) 1 Rigid (S2-5) 0 Mechanical pain 3 Yes No, but occasional non-mechanical pain 1 No, spinal metastasis is not associated with pain 0 Type of bone Lesion Lytic 2 Total score Spinal stability Mixed lytic and blastic 1 0–6 Stable 0 Blastic 7 – 12 Intermediate Subluxation/translation 4 Radiographic spinal 13 – 18 Unstable alignment 2 De novo deformity (kyphosis/scoliosis) 0 Normal Vertebral body (VB) >50% VB collapse 3 collapse <50% VB collapse 2 No collapse, but >50% VB involved 1 None of above 0 3 Involvement of the Bilateral posterolateral spinal Unilateral 1 elements None 0 Mechanical pain: pain that decreases when lying down and increases with movement or loading of the spine Involvement of the posterolateral spinal elements (facets, pedicle, costovertebral joint fracture or replacement with tumor) Stability factors Spinal location

Fig. 16.7. Spinal stability classification according to the Spinal Instability Neoplastic Score (SINS). (Modified from Fisher CG, DiPaola CP, Ryken TC, et al. (2010) A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine (Phila Pa 1976) 35: E1221–E1229.)

score. The OSRI includes two parameters (primary tumor pathology (PTP) and general condition (GC) determined by the KPS), with assigned weight from 0 to 5 points. The OSRI is calculated as follows: OSRI score ¼ PTP + (2 – GC). OSRI scores of 1 and 7 are associated with the longest (median survival: 23 months) and the shortest survival (median survival: 1 month), respectively (Balain et al., 2013).

The Spine Oncology Study Group defined neoplastic spinal instability as “loss of spinal integrity as a result of a neoplastic process that is associated with movementrelated pain, symptomatic or progressive deformity, and/or neural compromise under physiologic loads” and has designed the SINS (Fisher et al., 2010). SINS is based on six characteristics (location, pain, alignment, osteolysis, vertebral body collapse, and posterior-element

MANAGEMENT – SPINAL METASTASES involvement) and classifies the spinal lesion as stable (0–6 points), intermediate (7–12 points), and unstable (13–18 points). While surgical stabilization is recommended for unstable SINS, it should be considered for intermediate SINS (Figs 16.3 and 16.4). SINS has acceptable intra- and interobserver reliability (Fourney et al., 2011; Teixeira et al., 2013; Campos et al., 2014; Fisher et al., 2014; Arana et al., 2016). The development of prognostic models, such as a clinical prediction rules, is the first step in establishing such tools in clinical practice. Once created, any prognostic model needs to have its predictive performance empirically evaluated in distinct datasets to ascertain its predictive ability, i.e., validation phase (Adams and Leveson, 2012). To date, numerous prognostic models of survival for patients with MSD exist; while some are internally validated, a fewer number are externally validated. Of note, a systematic literature review revealed that most attempts to externally validate prognostic models were low-quality studies mostly due to poor design as well as inadequate statistical methods, including handling of missing data and failure to assess calibration, and overall reporting (Collins et al., 2014). Elaboration and validation of prognostic models require adherence to specific methodologic standards to reduce the risk of bias and thus potentiate their implementation in clinical practice. The predictive performance of a prognostic model is typically described by appraising its discrimination and calibration. Discrimination measures the model’s ability to separate patients with different responses or outcomes; the event rate should be higher in patients predicted to be at higher risk than those classified as being at lower risk. Discrimination is often assessed using the concordance (c) statistic. For binary outcome, such as survival or death, the c-statistic is identical to the area under the receiver operating characteristic curve. Calibration refers to the prediction accuracy or the extent of bias by identifying the degree of agreement between predicted and observed data. In a cohort of 1379 patients with symptomatic MSD in which 1141 patients (83%) received RT and 109 (8%) were treated with surgery and RT, although Bollen et al. (2016) did not assess calibration, they reported that the c-statistic was: 0.44 for the model by Rades et al. (2013); 0.64 for the models by Tokuhashi et al. (2005), Tomita et al. (2001), and Bauer and Wedin (1995); 0.66 for the model by van der Linden et al. (2005); and 0.69 for the model by Bollen et al. (2014) using an independent dataset (n ¼ 336) from the one that served to develop the model. That means that if this cohort of patients was to be separated into two groups, deceases and survivors, and 1 patient was randomly picked from each group, the Bollen model would correctly classify 69% of randomly drawn

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pairs. Although a few studies undertook to externally validate a specific prognostic tool (Bartels et al., 2007, 2016; Goodwin et al., 2016; Whitehouse et al., 2016), to our knowledge, there is no study externally validating all existing prognostic models in the same setting. As a result, there is a lack of evidence regarding the superiority of one prognostic model over another. Given that patients with MSD generally have a limited life expectancy, most prognostic tools have focused on survival to help guide physicians and patients in the therapeutic decision-making process. However, these scoring systems were developed from specific patient populations, which may limit their generalizability, and consequently, their clinical applicability. In addition, prognosis is only one of the key elements that are at play during therapeutic decision making. Therefore, although these prognostic tools may help guide physicians, none can substitute for clinical judgment. For MESCC patients, if the potential benefits are felt to outweigh the potential risk of morbidity and mortality associated with a specific intervention, preservation or improvement of the remaining quality of life is the cornerstone aspect to consider in the decision-making process.

ABBREVIATIONS cEBRT, conventional external-beam radiotherapy; ECOG, Eastern Cooperative Oncology Group; GC, general condition; KPS, Karnofsky Performance Status; MESCC, metastatic epidural spinal cord compression; MISS, minimally invasive spine surgery; MRI, magnetic resonance imaging; MSD, metastatic spinal disease; NOMS, Neurologic, Oncologic, Mechanical instability, and Systemic; OSRI, Oswestry Spinal Risk Index; PMMA, polymethylmethacrylate; PTP, primary tumor pathology; RT, radiotherapy; SBRT, stereotactic body radiation therapy; SINS, Spinal Instability Neoplastic Score

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