Table 1. Results of Treatment for Spinal Cord Compression: Radiotherapy Alone Authors Years Patients (n) % Motor % Worse

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1 Table 1. Results of Treatment for Spinal Cord Compression: Radiotherapy Alone Authors Years Patients (n) % Motor % Worse Improved Mones et al.[82] Khan et al.[83] Cobb et al.[84] Gilbert et al.[5] Marshall and Langfitt[77] Greenberg et al.[85] Stark et al.[86] Constans et al.[87] Obbens et al.[88] Harrison et al.[89] Bach et al.[90] Maranzano and Latini[78] Helweg-Larsen[91] Milross et al.[92] Katagiri et al.[93] Kovner et al.[94] Chamberlain and Kormanik[95] Kraiwattanapong et al. [96] Rades et al.[97] Rades et al.[98] Freundt et al.[99] Rades et al. [100] Rades et al.[101] Unweighted Mean (%) Weighted Mean (%) Total Patients 2251 Table 2. Results of Treatment for Spinal Cord Compression: Laminectomy with or without Radiotherapy Authors Years Patients % Motor % % Mortality (n) Improved Worse Hall & Mackay[102] Brady et al.[103] Merrin et al.[104] Cobb et al.[84] Gilbert et al.[5] Marshall &

2 Langfitt[77] Giannotta & Kindt[105] Kleinman et al.[106] Livingston & Perrin[107] Baldini et al.[108] Gorter[109] Dunn et al.[110] Levy et al.[111] Stark et al.[86] Constans et al.[87] Klein et al.[112] Kollmann et al.[113] Garcia-Picazo et al.[114] Bach et al.[90] Landmann et al.[115] Milross et al.[92] Schoeggl et al.[116] Rades et al.[101] Unweighted Mean (%) Weighted Mean (%) Total Patients 2098 Table 3. Results of Treatment for Spinal Cord Compression: Laminectomy (Posterior Decompression) and Stabilization Authors Years Patients (n) % Motor Improved % Pain Improved % Mortality Brunon et al.[117] Hansebout et al.[118] Miles et al.[119] DeWald et al.[36] Overby et al.[120] Solini et al.[121] Heller et al.[122] Perrin et al.[123] Olerud[124] Bauer[125] Bilsky[126] Chen et al.[127] Wang et al.[56] Arnold et al.[128] Jansson and

3 Bauer[72] Chen et al.[129] Cho et al.[130] Walter et al.[131] Unweighted Mean (%) Weighted Mean (%) Total Patients 1164 Table 4. Results of Treatment for Spinal Cord Compression: Vertebral Body Resection and Stabilization Authors Years Patients % Motor % Pain % Mortality (n) Improved Improved Slatkin and Posner[132] Harrington[133] Siegal and Siegal[134] Sundaresan et al.[135] Onimus et al.[136] Perrin & McBroom et al.[123] Moore & Uttley[137] Sundaresan et al.[138] Hall & Webb[139] Fidler[140] Hosono et al.[141] Gokaslan et al.[68] Weigel et al.[65] Chen et al.[69] Miller et al.[142] Heidecke et al.[143] Kan et al.[144] Alfieri et al.[145] Fang et al.[146] Knoeller et al.[147] Unweighted Mean (%) Weighted Mean (%) Total Patients 832 Table 5. Results of Treatment for Metastatic Spine Disease: Vertebroplasty Authors Years Patients (n) % Mobility Improved % Pain Improved % Pain Worse Kaemmerlen et al

4 [148] Cotten et al.[149] Weill et al.[150] Cortet et al.[151] Fourney et al.[152] Martin et al.[153] Alvarez et al.[154] Shimony et al.[155] Yang et al.[156] Yang et al.[157] McDonald et al [158] Tseng et al.[159] Sun et al.[160] Saliou et al.[161] Masala et al.[162] Mikami et al.[163] Farrokhi et al. [164] Unweighted Mean (%) Weighted Mean (%) Total Patients 864 Table 6. Results of Treatment for Metastatic Spine Disease: Kyphoplasty Authors Years Patients (n) % Mobility Improved % Pain Improved % Pain Worse Dudeney et al.[165] Fourney et al.[152] Vrionis et al.[166] Pflugmacheret al.[167] Pflugmacher et al.[168] Zou et al.[169] Dalbayrak et al.[170] Chen et al.[171] Berenson et al.[39] König et al. [172] Unweighted Mean (%) Weighted Mean (%) Total Patients 277

5 Table 7. Results of Treatment for Metastatic Spine Disease: Stereotactic Radiosurgery (SRS) Authors Years Patients (n) Local Tumor Control Rate % Pain Improved % Pain Worse (%) Ryu et al.[173] Ryu et al. [53] Benzil et al.[174] Gerszten et al.[52] Degen et al.[175] Gerszten et al.[176] Gerszten et al.[177] (lung) Gerszten et al.[178] Gibbs et al.[179] Wowra et al.[54] Ryu et al.[180] Tsai et al.[181] Sheehan et al.[182] Choi et al.[183] Lee & Chun[184] Unweighted Mean (%) Weighted Mean (%) Total Patients 1028 Table 8. Median Postoperative Survival Based on Tumor Pathology Tumor Pathology Lung* Lung (squamous cell)** Multiple myeloma Prostate*** Breast**** Breast/prostate* Melanoma***** Renal* Hopkins Median survival after surgery (months) Other Median Timing of Cohorts survival after surgery (months)

6 Other data: *Lee 2012; includes thyroid, breast, prostate, carcinoid tumor for 5 point cancers, renal and uterus for 3 point cancers, and lung, osteosarcoma, stomach, bladder, esophagus, pancreas for 0 point cancers[64] **Wachtel 2012[185] *****Weigel 1999; groups lung carcinoma and melanoma patients together[65] Hopkins data: unpublished multiple myeloma data ***Ju 2013; prostate data[61] ****Zadnik 2013;breast data[59]

7 Supplementary Table. Level of Evidence for Studies Citation Description of Study Evidence Level Toma, J Surg Oncol, 2007[4] Tomita, Spine, 2001[17] A retrospective review and trend-analysis of all cases with metastatic bone disease admitted to a single tertiary orthopedic referral center, between 1968 and 2003, was conducted. Retrospective evaluation of 67 patients with spinal metastases ( ) and their prognostic factors to develop a new scoring system for spinal metastases. Afterwards, 61patients were treated prospectively according to this surgical strategy ( ). Conclusions Over the 36-year period, the frequency of bone metastases has increased at the center. Although survival increased over time, the difference was not significant, most likely attributable to the seriousness of cases referred to tertiary care center. A new surgical strategy for spinal metastases based on the prognostic scoring system is proposed and provides appropriate guidelines for treatment in all patients with spinal metastases. Tokuhashi, Spine, 2005[18] Saillant, Rev Chir Orthop Reparatrice Appar Mot, 1995[76] Patchell, Lancet, 2005[37] Wang, J Neurosurg Spine, 2004[56] Gokaslan, J Neurosurg, 1998[68] Sundaresan, J Neurosurg, 1996[44] Semi-prospective study involving 164 patients who died after surgery and 82 who died after conservative treatment seeing to evaluate whether revised scoring system accurately predicted survival. Case Series: Retrospective study of 37 patients with spinal metastasis of thyroidal origin treated from Randomized, multi-institutional, non-blinded trial randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Case Series: 140patients with spine metastases underwent the posterolateral transpedicular approach (PTA) to decompress the spine circumferentially and to place instrumentation ( ). Case Series: outcomes in 72 patients with metastatic thoracic spinal tumors who were treated by transthoracic vertebrectomy. Case Series: analysis of outcomes in 110 patients who underwent surgery for primary and metastatic The prognostic criteria using the total scores from the revised Tokuhashi scale were useful for the pretreatment evaluation of metastatic spinal tumor prognosis irrespective of treatment modality or local extension of the lesion. The most radical therapeutic option should be chosen for vertebral metastases of thyroidal origin. The importance of the tumoral reduction is connected with the efficiency of the iodiotherapy (for differentiated histological types); this is a considerable adjuvant treatment for this kind of cancer. Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer. The PTA allows circumferential epidural tumor decompression and the placement of anterior and posterior spinal column instrumentation. Immediate spinal stability is achieved without the use of brace therapy. The PTA achieved a high success rate for pain palliation, neurological preservation, and functional improvement, while avoiding the morbidity associated with combined approaches. Transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality. Despite the high incidence of complications, majority of patients

8 Berenson, Lancet Oncol, 2011[39] Maranzano, Int J Radiat Oncol Biol Phys.,1995[78] Simmonds, BMJ, 2000[80] Levack, Clin Oncol (R Coll Radiol), 2002[186] Molina, International Journal of Surgical Oncology, 2011[42] Sze, Cochrane Database Syst Rev, 2004[46] spinal ( ). Multicenter randomized controlled trial: 134 patients were enrolled and randomly assigned to kyphoplasty (n=70) or non-surgical management (n=64). 65 patients in the kyphoplasty group and 52 in the control group had data available at 1 month. Comparative study: prospectively assessed outcomes in 275 patients with metastatic spinal cord compression, specifically, radiotherapy (255) or surgery plus radiotherapy (20). Systemic Review/Meta-analysis of Class Studies: meta-analysis of seven randomized controlled trials that provided individual patient data (866 patients) to determine benefits/harms of palliative chemotherapy in locally advanced or metastatic colorectal cancer patients and to compare the outcomes for elderly and younger patients Case Series: prospective observational study examined the diagnosis, management and outcome of 319 patients diagnosed with metastatic spinal cord compression ( ). The process was considered from the perspectives of the patient, the general practitioner, and the hospital doctor. Systemic Review of Class Studies: evaluating the clinical efficacy and safety of minimally invasive surgery (MIS) in the setting of metastatic spine disease. Systematic review/meta-analysis: Comparing single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications. reported improvement in their quality of life at follow-up review. Findings suggest that half of all patients with spinal malignancies require combined anteriorposterior surgery for adequate tumor removal and stabilization. For painful vertebral compression fractures in patients with cancer, kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function. Early diagnosis of MSCC is a powerful predictor of outcome. Radiation therapy plus steroids in MSCC is effective. Most important factors for positively conditioning results are: the high rate of early diagnoses, the number of tumors with favorable histologies recruited, and the choice of best treatment based on appropriate patient selection for surgery and RT or RT alone. Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated in this analysis as some patients in the control arms received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Patients with cancer who describe severe back or spinal nerve root pain need urgent assessment on the basis of their symptoms, as signs may occur too late. Plain films and bone scans requested for patients in this audit predicted accurately the level of compression in only 21% and 19% of cases, respectively. The only accurate investigation to establish the presence and site of a compressive lesion is magnetic resonance imaging. MIS is an efficacious means of achieving neurological improvement and alleviating pain. MIS offers decreased blood loss, operative time, and complication rates in comparison to standard open spine surgery. However, due to the paucity of studies and low class of available evidence, the ability to draw comprehensive conclusions is limited. Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological

9 Chow, J Clin Oncol, 2007[47] Wu, Int J Radiat Oncol Biol Phys, 2003[48] Mithal, Int J Radiat Oncol Biol Phys, 1994[49] Lau, Eur Spine J, 2013[67] Systematic review: updating previous meta-analyses with a systematic review of randomized palliative radiotherapy trials comparing single fractions versus multiple fractions. Meta-analysis: comparing pain relief among various dose-fractionation schedules of localized radiotherapy (RT) in the treatment of painful bone metastases. Case Series: retrospective analysis of consecutive patients treated with palliative radiotherapy for painful bone metastases. Case Series: retrospective review and multivariate analysis of patients who underwent surgery for spinal metastases to assess independent predictors of perioperative and postoperative adverse events. Chong, Spine J, 2012[71] Case Series: retrospective observational study of 104 patients who underwent single-stage posterior decompression and stabilization (PDS) with or without corpectomy for metastatic spinal cord compression (MSCC) of the thoracic spine to assess treatment outcomes and determine relationship between functional outcomes and the survival. Jansson, Eur Spine J, 2006[72] Kwon, Yonsei Med J, 2009[73] Case Series: prospective study of 282 spinal metastases patients who underwent surgical treatment to assess survival, neurological function, and complications. Comparative Study: retrospectively investigating whether primary malignancy entities and the extent of tumor resection have an effect on the survival rate and neurological improvement in patients with spinal fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option. No significant differences in the arms were observed for overall and complete response rates in both intention-to-treat and assessable patients. However, a significantly higher re-treatment rate with single fractions was evident. There is no significant difference in complete and overall pain relief between single and multifraction palliative RT for bone metastases. No dose-response relationship could be detected by including data from the multifraction vs. multifraction trials. Additional data are needed to evaluate the role of reirradiation and the impact of RT on other treatment end points such as quality of life. In patients relapsing after radiotherapy to painful bone metastases who have responded initially, reirradiation can be recommended with a similar probability of response. Patients older than 40 years or patients who have metastatic lesions involving three or more contiguous vertebral levels appear to be at higher risk for complication. Patients older than 65 years have the greatest likelihood of complication. Single-stage posterior decompression and stabilization with or without corpectomy effectively improved the functional status of patients with MSCC of the thoracic spine and also afforded the patients to have more chances of postoperative adjuvant therapy, which was significant for patients' survival. The role of surgery in the management of MSCC could be not only a symptomatic palliation but also a strategy to prolong patients' survival. Improvement of function can be gained by surgical treatment, but the complication rate was high and many patients died of their disease within the first months of surgery. Individuals who underwent gross total resection of tumors that responded to adjuvant therapy showed a higher survival rate than those who underwent

10 Gerszten, J Neurosurg Spine, 2005[41] Cotten, Radiology, 1996[149] Weill, Radiology, 1996[150] Dalbayrak, J Clin Neurosci, 2010[170] metastases that extend beyond the vertebral compartment. Case series: evaluating a treatment paradigm of closed fracture reduction and fixation involving kyphoplasty and subsequent spinal radiosurgery; prospective study of 26 patients (6 men, 20 women, mean age 72 years) with pain due to pathological compression fractures (16 thoracic and 10 lumbar). Case series: prospective study assessing whether percentage of vertebral lesion filling and leakage of methylmethacrylate have clinical significance at follow-up; 40 percutaneous vertebroplasties were performed for metastases (30 cases) and myeloma (10 cases) in 37 patients. Case Series: assessing efficacy of percutaneous vertebroplasty in treating spinal metastases that result in pain or instability in 37 patients (20 men, 17 women; aged years). Case Series: assessing the clinical and radiological results after kyphoplasty in 31 patients with vertebral body compression fractures due to spinal metastasis and multiple myeloma and to determine factors that may affect outcome. subtotal resection. For tumors not responding to adjuvant therapy, palliative surgical decompression is suggested. Combined kyphoplasty and spinal radiosurgery treatment paradigm was found to be clinically effective in patients with pathological fractures; there was no significant spinal canal compromise. This combination avoids the morbidity associated with open surgery while providing both immediate fracture fixation and administering a singlefraction tumoricidal radiation dose. Pain relief can occur despite insufficient lesion filling. In most patients, intradiskal and paravertebral leaks of cement had no clinical importance. Vertebroplasty of metastases is a minimally invasive procedure that provides immediate and long-term pain relief and contributes to spinal stabilization. Kyphoplasty is safe and effective for treating painful vertebral body fractures caused by metastasis and multiple myeloma. It can restore vertebral body height and correct the kyphosis angle. Increased amount of the injected PMMA led to leakage, and did not contribute to restoration of the vertebral body height or kyphosis correction; injecting excessive amounts of PMMA should be avoided. Fourney, J Neurosurg, 2003[152] Chen, Arch Orthop Trauma Surg, 2000[69] Ryu, J Neurosurg, 2004[53] Case Series: retrospective study assessing the safety and efficacy of vertebro- and kyphoplasty for painful vertebral body fractures in cancer patients in a consecutive group of cancer patients (21 with myeloma and 35 with other primary malignancies). Case Series: assessing anterior corpectomy with Zielke instrumentation on pain relief, spinal stability, and neurologic function in 60 consecutive patients ( ) with spinal metastasis age 21 to 76 years (mean: 54 years). Case Series: retrospective assessment of 49 patients with 61 solitary spinal metastases who Percutaneous vertebro- and kyphoplasty provided significant pain relief in a high percentage of patients, and this appeared durable over time. The absence of cement leakage-related complications may reflect the use of 1) high-viscosity cement; 2) kyphoplasty in selected cases; and 3) relatively small volume injection. Precise indications for these techniques are evolving; however, they are safe and feasible in well-selected patients with refractory spinal pain due to myeloma bone disease or metastases. Anterior corpectomy to decompress neural encroachment with instrumental reconstruction to stabilize the collapsed spine is a good adjunctive treatment in these highly selected patients. Spine-related pain control/reduction is excellent. Tumor recurrence at the treated

11 Fourney, J Clin Oncol., 2011[31] underwent radiosurgery ( ) to determine patterns of failure after spinal radiosurgery. Validity Study: determining the interobserver reliability, intraobserver reliability, and predictive validity of the Spinal Instability Neoplastic Score (SINS). I segment and progression to the immediately adjacent region were rare. The results support the use of spinal radiosurgery as an effective treatment option for solitary spinal metastasis. SINS demonstrated near-perfect interand intraobserver reliability in determining three clinically relevant categories of stability. The sensitivity and specificity of SINS for potentially unstable or unstable lesions were 95.7% and 79.5%, respectively. Ryu, Cancer, 2003[173] Benzil, J Neurosurg, 2004[174] Gerszten, Cancer, 2005[176] Degen, J Neurosurg Spine, 2005[175] Gerszten, Stereotact Funct Neurosurg, 2005[176] Case Series: assessment of accuracy and precision of intensity-modulated radiosurgery in 10 patients with metastatic spine tumors (2001). Case Series: assessment of initial experience with stereotactic radiosurgery of the spine with regard to dose, efficacy, and toxicity for 31 patients with metastatic spine tumors ( ) Case Series: prospective assessment of the clinical efficacy of single-fraction radiosurgery for treatment of spinal breast carcinoma metastases in 50 patients with a follow-up period of 6 48 months, median 16 months. Case Series: assessment of safety, pain, and quality of life (QOL) outcomes following CyberKnife radiosurgical treatment of spinal tumors in 51 patients ( ). Case Series: assessment of clinical efficacy of SRS in 28 patients with melanoma spine metastases ( ). Image-guided, shaped-beam spinal radiosurgery is accurate and precise. Rapid clinical improvement of pain and neurologic function may be achieved. Spinal radiosurgery can be used to treat patients with spinal metastasis, especially those with solitary sites of spine involvement, to increase the prospects of long-term palliation. Stereotactic radiosurgery of the spine is safe at the doses used and provides effective pain relief. In this study, biologically equivalent doses greater than 60 Gy were associated with an increased risk of radiculitis. Spinal radiosurgery was found to be feasible, safe, and clinically effective for the treatment of spinal metastases from breast carcinoma. Radiosurgery can treat patients with spinal breast metastases, especially those with solitary sites of spine involvement, to improve long-term palliation. CyberKnife radiosurgery improves pain control and maintains QOL in patients treated for spinal tumors. Early adverse events are infrequent and minor. SRS safely delivers large dose fractions of radiation therapy in a single fraction for the management of spinal metastases in patients with advanced melanoma that are often poorly controlled with alternative conventional external beam radiation therapy. It is successful even in patients with previously irradiated lesions. Gerszten, Cancer, 2006[177] Case Series: prospective assessment of efficacy of single-fraction radiosurgery technique with a followup period of 6 to 40 months (median, 12 months). SRS was found to be feasible, safe, and clinically effective for the treatment of spinal metastases from lung cancer. SRS can treat spinal lung metastases,

12 especially solitary sites of spine involvement, to improve long-term palliation. Gerszten, Spine, 2007[178] Case Series: assessment the clinical outcomes of single-fraction radiosurgery as part of the management of metastatic spine tumors for 294 patients. Radiosurgery can treat patients with spinal metastases, especially those with solitary sites of spine involvement, to improve long-term palliation. Gibbs, Radiother Oncol, 2007[179] Case Series: determining the effectiveness and safety of image-guided robotic radiosurgery (CyberKnife) for spinal metastases in 74 patients ( ). Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients. Wowra, Spine, 2008[54] Case Series: prospective assessment of clinical results of CyberKnife fiducial-free spinal radiosurgery in 102 consecutive patients with no more than 2 malignant spinal tumors ( ). Spinal radiosurgery is a noninvasive, safe, and effective treatment method for patients with 1 or 2 small spinal malignant tumors. The best benefit of the treatment can be expected in patients with good to excellent clinical condition and patients with severe tumor associated pain. Ryu, J Pain Symptom Manage, 2008[180] Tsai, J Neurooncol, 2009[181] Case Series: assessment of clinical efficacy of spine radiosurgery for the treatment of solitary spinal metastases with or without cord compression in 49 patients ( ). Case Series: assessment of clinical efficacy of SRS in 69 consecutive patients with thoracic and lumbar metastatic tumors ( ). SRS can achieve rapid and durable pain relief. Single-dose radiosurgery has a potential to be a viable treatment option for single spinal metastasis. CyberKnife radiosurgery is a welltolerated and effective treatment for spine tumors with good local tumor control and a favorable outcome on pain and functional improvement after treatment. Sheehan, Neurosurgery, 2009[182] Choi, Int J Radiat Oncol Biol Phys, 2010[183] Case Series: retrospective assessment of effectiveness and limitations of SRS using a helical TomoTherapy system for the treatment of spinal metastases in 40 patients. Case Series: retrospective assessment of SRS in treatment of spinal metastases recurring in previously irradiated fields in 42 patients ( ). Radiosurgery is effective as either primary or adjunctive treatment of metastatic tumors of the spine. SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). More research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose. Lee, Tumori, 2012[64, 184] Dudeney, J Clin Oncol., 2002[165] Case Series: retrospective assessment of SRS in addressing pain relief for 57 patients ( ) with spinal metastases, and analysis of factors associated with pain relapse after initial pain relief. Case Series: prospective evaluation of the safety and efficacy of kyphoplasty in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma in 18 patients. As previous studies have shown, pain relief with spinal radiosurgery is around 90%. In particular, long-term pain relief and disease control was observed in patients with solitary spinal metastasis. Kyphoplasty is efficacious in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. Kyphoplasty is

13 associated with early clinical improvement of pain and function as well as some restoration of vertebral body height. Vrionis, Techniques in Regional Anesthesia and Pain Management, 2005[166] Pflugmacher, Acta Radiol, 2006[167] Case Series: retrospective assessment of kyphoplasty for painful compression fractures of the thoracic and/or lumbar spine resulting from spinal metastases in 50 patients. Case Series: evaluation of clinical and radiographic outcomes of balloon kyphoplasty in 20 patients with fractures of the thoracic and lumbar spine caused by multiple myeloma. Kyphoplasty can be a safe and beneficial procedure in cancer patients who present with painful compression fractures of the spine. Balloon kyphoplasty is an effective minimally invasive procedure for stabilizing pathological vertebral fractures caused by multiple myeloma and significantly reducing pain. Balloon kyphoplasty stabilizes the vertebral body height, but is only partially able to prevent further kyphotic deformities. Pflugmacher, Acta Radiol, 2007[168] Case Series: evaluation of clinical and radiographic outcomes of balloon kyphoplasty in 31 patients with fractures of the thoracic and lumbar spine caused by metastatic disease. Balloon kyphoplasty is an effective, minimally invasive procedure for the stabilization of pathological vertebral fractures caused by metastatic disease. It gives a significantly reduces pain and prevents further kyphotic deformity of the spine. Zou, J Surg Oncol, 2010[169] Case Series: assessment of clinical and radiographic outcomes of kyphoplasty in 21 patients with fractures caused by multiple myeloma. Kyphoplasty is a safe and clinically effective treatment for pathologic vertebral fractures from multiple myeloma, even in levels with vertebral wall deficiency. The strategy of determining systematic level by alterations in MRI signal is effective in lowering the cost. Chen, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2011[171] Case Series: evaluating the diagnosis and effectiveness of improved percutaneous kyphoplasty (PKP) for 16 patients with thoracolumbar metastatic tumors, who could not tolerate anesthesia and open operation ( ). For patients with thoracolumbar metastatic tumors who cannot tolerate anesthesia and open operation, improved PKP has the advantages such as minimal invasion, high diagnostic rate, and early improvement of pain in the biopsy and treatment; it can improve patient's quality of life in the combination of radiotherapy or chemotherapy. König, Eur Spine J, 2012[172] Case Series: prospective assessment of the efficacy and safety of percutaneous kyphoplasty in 11 patients with osteolytic tumors of the thoracic and lumbar spine. Kyphoplasty is a suitable palliative treatment option for patients with advanced metastatic disease of the spine even with low Tokuhashi scores allowing rapid pain relief and mobilization to increase the quality of life. Kaemmerlen, J Radiol, 1989[148] Case series: evaluating clinical efficacy of percutaneous vertebroplasty (PVP) in 20 patients with vertebral metastases. The best indication for vertebroplasty is the painful somatic lysis of a vertebra without peri-radicular tumor. Cortet, Rev Rhum Engl Ed, 1997[151] Case Series: evaluating short- and medium-term outcomes of vertebroplasty in 37 metastatic spine disease patients with severe or excruciatingly severe Vertebroplasty is simple and effective for the treatment of osteolytic metastases and multiple myeloma lesions, but should be

14 pain, unresponsive to narcotics. performed only in centers with neurosurgical and/or orthopedic surgery units because of the possibility of severe complications. Martin, Radiology, 2003[153] Alvarez, Eur Spine J, 2003[154] Case series: assessing the clinical effectiveness of percutaneous vertebroplasty in 32 consecutive patients with pedicle lysis ( ). Case series: retrospective assessment of 21 consecutive patients undergoing percutaneous vertebroplasty for of vertebral metastases, especially with respect to functional outcome. This safe technique allows for clinically effective pain relief, and in contrast to other access routes, the direct treatment of the lysed pedicles. PMMA proved to be safe and beneficial, providing significant and early improvement in the functional status of patients with spinal metastasis. Shimony, Radiology, 2004[155] Case series: evaluation of safety and effectiveness of percutaneous vertebroplasty in 50 patients with malignant compression fractures and involvement of the epidural space ( ). PVP can be performed safely and effectively with conscious sedation in patients with malignant compression fractures and epiduralinvolvement. Yang, Chinese Journal of Clinical Oncology, 2005[156] Comparative Study: exploring the clinical effect in 55 patients with metastatic spinal tumors treated by percutaneous vertebroplasty under the guidance of digital subtraction angiography (DSA ) + chemotherapy vs control group (chemotherapy and radiation therapy). PVP is a simple operation causing only small wounds and few complications. It can effectively alleviate pain of metastatic spinal tumors in patients, improve quality of life and reduce the incidence rate of paraplegia. Yang, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2006[157] Case series: retrospective analysis of the clinical therapeutic effects of percutaneous vertebroplasty under the guidance of the digital subtraction angiography (DSA) on malignant spinal tumors in 196 patients ( ). PVP under the guidance of the DSA is an easier operation with a small wound and few complications. It can effectively alleviate the patient's pain due to metastatic spinal tumor, stabilize the spine, improve the patient's quality of life, and reduce the incidence of paraplegia. McDonald, AJNR Am J Neuroradiol,2008[158] Tseng, Surg Neurol, 2008[159] Case Series: retrospective review characterizing the imaging characteristics, clinical course, and outcomes in 67 myeloma patients treated with vertebroplasty. Case Series: assessment of clinical effects in 57 patients with spinal metastatic tumor treated with PMMA vertebroplasty ( ). Vertebroplasty provides significant and durable pain relief for patients with intractable spinal pain secondary to compression fractures resulting from multiple myeloma. Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications. Sun, Technol Cancer Res Treat, 2010[160] Case Series: retrospective study evaluating the feasibility, safety, and efficacy of PVP for the C2 osteolytic metastases using anterolateral and posterolateral approaches in 10 patients. PVP of C2 using anterolateral approach is a feasible and minimal invasive procedure for treatment of patients with C2 osteolytic metastases. Posterolateral approach is a safe and effective option for PVP of C2 when hyperextension of the cervical spine is contraindicated or difficult to achieve. Saliou, Radiology, 2010[161] Case Series: evaluating the feasibility, efficacy, and safety of percutaneous vertebroplasty in the treatment of pathologic fractures owing to malignancy with epidural involvement, with or without neurologic The feasibility, efficacy, and safety of PVP were confirmed in patients experiencing pain related to malignant spinal tumors with epidural extension,

15 symptoms of spinal cord or cauda equina compression, in 51 patients. with a low complication rate. PVP should become part of the palliative analgesic treatment for such patients. Masala, Clin Orthop Relat Res, 2011[162] Case Series: retrospective study evaluating technical feasibility, complication rate, and ability of percutaneous vertebroplasty to provide pain relief in 62 patients with painful metastatic cervical fractures ( ). PVP may be performed with a high technical success rate combined with a low complication rate, providing immediate pain relief lasting at least 3 months and a reduction in the use of analgesic drugs. Mikami, Jpn J Radiol, 2011[163] Case Series: retrospective study investigating the therapeutic effects of percutaneous vertebroplasty on vertebral metastases in 69 patients ( ). PVP can offer pain relief to patients with painful vertebral metastases and short life expectancy whose general condition makes surgery difficult. Farrokhi, Iran Red Crescent Med J, 2012[164] Case Series: assessing pain-relief efficacy of percutaneous vertebroplasty in 25 patients with spinal fractures due to metastatic spinal tumors. Considering significant decrease in the mean pain severity degree after the treatment, vertebroplasty seems to be significantly effective in pain relief in metastatic spinal tumors. Slatkin, Clin Neurosurg, 1983[132] Harrington, J Neurosurg, 1984[133] Case Series: assessing clinical effects of vertebral body resection and stabilization in 29 patients with spinal epidural metastases. Case Series: assessing anterior decompression and stabilization by replacement of the affected vertebral bodies with methyl methacrylate in 52 patients with spinal instability secondary to metastatic pathological fractures of one or more vertebrae. Vertebral body resection and stabilization resulted in improved motor and pain scores; it may be an effective modality in treating those with spinal epidural metastases and compression. This procedure offered good relief of pain and restoration of spinal stability, which did not deteriorate during the follow-up period, ranging from 6 to 100 months postoperatively. Siegal, Neurosurgery, 1985[134] Case Series: prospective treatment of 167 episodes of spinal epidural neoplastic compression in 86 patients (61 vertebral body resections, 25 laminectomies). Vertebral body resection and stabilization resulted in improved motor and pain scores; it may be an effective modality in treating those with spinal epidural compression. Sundaresan, J Neurosurg, 1985[135] Case Series: evaluation of vertebral body resection and immediate stabilization for neoplastic spinal cord compression in 101 consecutive patients. Surgery prior to irradiation is indicated in selected patients with neoplastic cord compression. In patients with solitary osseous metastasis to the spine, potentially curative resection can be undertaken if surgery is performed when the tumor is still confined to the vertebral body. Onimus, Spine, 1986[136] Case Series: evaluation of 57 patients with spinal metastases; 36 patients were operated on by anterior approach with decompressive corpectomy and stabilization by metal and methylmethacrylate and 24 patients by laminectomy and/or stabilization by osteosynthesis. Surgery is beneficial and should be preferred to radiation when there is medullary compression by corporal metastasis and also in the presence of intense pain or potential instability of the spine. Perrin, Can J Neurol Sci, 1987[123] Comparative Study: evaluation of anterior and posterior decompression in patients with metastatic spinal cord compression. The optimal surgical approach, whether from in front or from behind is determined by a number of factors including (1) tumor location, (2) spinal

16 level, (3) fixation factors, (4) patient debility. Moore, Neurosurgery, 1989[137] Case series: prospective evaluation of 26 consecutive patients with neurological complications of neoplastic epidural cord compression undergoing anterior decompression followed by stabilization in a single stage procedure. The method is recommended, for selected patients, for the management of cord compression caused by collapse of the vertebral body. The patient's prospects of restored ability to walk after a single-stage operation are good, and the risk of adverse neurological effects is negligible. Sundaresan, Neurosurgery, 1991[138] Case Series: prospective evaluation of 54 patients with neoplastic spinal cord compression to determine the role of de novo surgery in patients with spinal metastases. Surgery and adjuvant therapy resulted in better outcomes than after external radiation therapy and steroids alone; these results suggest that de novo surgery be considered in selected patients with spinal metastases. Hall, Spine, 1991[139] Case Series: clinical evaluation of 15 patients with tumor involvement of the cervical or thoracic spine and neurologic deficit treated by single-stage anterior decompression and AO plate stabilization. Standard AO plates provide adequate stabilization of the cervical and thoracic spine after vertebrectomy for tumor involvement. Fidler, J Bone Joint Surg Br, 1986[140] Case Series: evaluation of anterior decompression followed by stabilization in 17 patients with compression of the spinal cord and/or severe pain and pathological fractures of the thoracolumbar spine which had not responded to conservative treatment. Anterior compression of the thoracolumbar spinal cord due to pathological fracture should be treated by anterior decompression when conservative treatment is ineffective. The sooner this is performed, the better the recovery. Stability can be restored by anterior instrumentation below T2 and posterior instrumentation above that level. Ancillary treatment-radiotherapy, chemotherapy and hormones should be included in the management scheme whenever indicated. Hosono, Spine, 1995[141] Case Series: retrospective assessment of the clinical outcome of vertebral replacement surgery with unique ceramic prosthesis for spinal metastases in 84 patients. In selected patients, vertebral replacement using the ceramic prosthesis proved to be a useful procedure, effectively managing the severe spinal pain or neurologic deficits associated with vertebral body destruction. Gokaslan, J Neurosurg, 1998[68] Case Series: evaluation of anterior vertebral body resection, reconstruction, and stabilization for spinal metastases limited to the thoracic region in 72 patients. Transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality. Weigel, Spine, 1999[65] Case Series: retrospective evaluation of postoperative outcome and quality of life in 76 consecutive patients surgically treated for symptomatic spinal metastases. Surgical management of symptomatic spinal metastases, in particular anterior decompression, is of benefit in most metastatic lesions in terms of satisfactory

17 postoperative outcome and quality of life. However, in patients with melanoma or lung carcinoma, the authors advocate spinal surgery only in very exceptional cases. Miller, J Neurosurg, 2000[142] Case Series: retrospective assessment of efficacy and stability of polymethylmethacrylate anterior surgical constructs in conjunction with anterior cervical plate stabilization in 29 patients with spinal metastasis. The anterior, coaxial, double-lumen, PMMA reconstruction technique provides a simple means of spinal cord protection in patients in the supine position while undergoing surgery and offers excellent results in cancer patients who have undergone cervical vertebrectomy. Heidecke,Acta Neurochir, 2003[143] Case Series: retrospective study summarizing the long-term results of surgery and the outcome of 62 patients with cervical spine metastases who underwent instrumented spinal surgery ( ). Surgical removal of epidural metastases with subsequent instrumented fusion is a low-morbidity and low-complications procedure with high rates of permanent stabilization of the compromised cervical spine. It also improves the neurological deficits and relieves the local pain. Excellent local control of malignant disease can be achieved by the surgical procedure aided by subsequent local and systemic adjuvant therapy. Overall survival time and prognosis of the patients, however, mainly depend on the type and the stage of the primary malignancy. Alfieri, Clin Neurol Neurosurg, 2011[145] Case Series: evaluation of a 6 consecutive patients who underwent to resection of metastatic tumor in the cervical spine followed by expandable cylindrical cage reconstruction of the anterior vertebral column ( ). Expandable cylindrical cages are effective resources for functional reconstruction after tumor resection in patients with cervical metastasis with advantages in the quality of life. Kan, Neurosurg Focus, 2008[144] Case Series: an evaluation of the minimally invasive thoracoscopic approach for the surgical treatment of thoracic and thoracolumbar metastatic spinal cord compression in 5 patients with metastatic disease of the thoracic spine, including the thoracolumbar junction. Minimally invasive thoracoscopic approach can be applied to the treatment of thoracic and thoracolumbar metastatic spine disease in an effort to reduce access morbidity. Preliminary results have indicated that adequate decompression, reconstruction, and stabilization can be achieved with this technique. Fang, J Neurosurg Spine, 2012[146] Comparative Study: comparing surgical outcomes of the mini-open anterior corpectomy procedure with that of the posterior total en bloc spondylectomy (TES) in 41 total patients with solitary metastases of the thoracolumbar spine. Mini-open anterior corpectomy can be accomplished with less blood loss, fewer fixation instrumentations, and shorter surgical time than that required for TES, but patients who undergo a mini-open corpectomy may have a greater tendency to experience local recurrence. A miniopen anterior corpectomy has a relatively mild learning curve and involves fewer technical difficulties. With smaller incisions, mini-open anterior corpectomy is an option in treating solitary

18 metastases of the thoracolumbar spine. Knoeller, Int Orthop, 2012[147] Case Series: evaluation of the clinical results for a single-stage anterior decompression with corpectomy defect restoration with titanium cage and single double rod system in 45 patients suffering from vertebral metastases with spinal stenosis, instability and/or neurological deficits secondary to pathological lumbar spine fractures and bone mineral density 1.20 g/cm 2. In lumbar spine fractures of metastatic origin with stenosis, instability and/or neurological deficit, a single stage ventral decompression and instrumentation in patients with bone mineral density 1.20 g/cm 2 should be considered. Brunon, Neurochirurgie, 1975[117] Case Series: evaluation of clinical outcomes for decompressive surgical removal of tumor through laminectomy, associated with a bilateral posterior metallic osteosynthesis in 23 patients (20 with a metastatic tumor and 3 with a plasmocytoma). This combine procedure, by consolidating the spine, relieving pain and consequently allowing kinesitherapy to be resumed earlier, is able to improve the functional status and increase survival of the patients. Hansebout, J Neurosurg, 1980[118] Case Series: evaluating clinical outcomes of spinal fusions using acrylic performed in 82 patients, most of whom had metastatic disease involving the epidural space ( ). Acrylic-wire fusion provides rapid spinal stabilization for patients whose prognosis is limited and whose quality of life might otherwise be compromised by bracing and prolonged hospitalization. The results in this clinical indicate that acrylic-wire fusion is a useful operative stabilization technique in selected patients. Miles, J Neurol Neurosurg Psychiatry, 1984[119] Case Series: the clinical outcomes in 26 patients (23 spinal metastases, 3 primary tumor) who underwent posterior decompression and stabilization were evaluated. Posterior decompression and stabilization can offer pain relief and neurological improvement in patients with spinal tumors. DeWald, Spine, 1985[36] Case Series: retrospective review of 17 patients with metastatic spine disease receiving posterior decompression and stabilization. Surgery offered spinal stability, pain relief, and neurological improvement. Also, a classification for treatment purposes regardless of tissue type was developed. Once classified, the surgical goals for these patients were to decrease pain, to preserve or to improve neurologic function and to mobilize the patient without external orthosis. Overby, J Neurosurg, 1985[120] Case Series: assessing 12 patients with epidural spinal cord compression from metastatic carcinoma that have been treated surgically by a modified costotransversectomy approach for anterolateral decompression. Anterolateral decompression by a modified costotransversectomy approach should be considered for management of ventrally located tumors or when posterior stabilization is considered a possible requirement following a proposed anterior decompression. Solini, Ital J Orthop Traumatol, 1985[121] Case Series: evaluation of posterior decompression and stabilization in 33 patients affected by metastases in the lumbar spine. In patients with neurological deficit, early surgery is more beneficial. Surgery may also be helpful in preventing further neurological damage. Heller, Neuroorthopedics, Case Series: evaluation of posterolateral decompression and stabilization with Luque Posterolateral decompression and stabilization appears effective in

19 1986[122] instrumentation in 33 patients with spinal metastases. providing pain relief and neurological improvement in select patients. Olerud, Acta Orthop Scand, 1996[124] Bauer, J Bone Joint Surg Am, 1997[125] Bilsky, Spine, 2000[126] Chen, Chang Gung Med J, 2004[127] Arnold, The Spine Journal, 2004[128] Jansson and Bauer, Eur Spine J, 2006[72] Chen, Spine, 2007[129] Cho,Surg Neurol, 2009[130] Case Series: prospective evaluation of 51 patients with spinal metastases undergoing posterior decompression and fixation. Case Series: assessment of neurological function, survival, and rehabilitation of sixty-seven consecutive patients who had been treated with decompressive surgery for spinal metastatic epidural compression. Case Series: retrospective assessment of 25 spinal metastases patients operated on using a posterolateral transpedicular approach. Case Series: investigation of the clinical results of posterior decompression and stabilization for metastatic diseases of the thoracolumbar spine in 70 consecutive patients ( ). Case Series: evaluation of 73 spinal metastases patients who underwent posterior decompression, fixation, and fusion. Case Series: assessment of survival, neurological function, and complications in a consecutive series of 282 patients operated for spinal metastases ( ). Case Series: retrospective evaluation of palliative surgery using a posterolateral transpedicular approach (PTA) or combined posterior and anterior procedures in 31 consecutive patients with nonsmallcell lung cancer (NSCLC) with symptomatic spinal cord compression ( ). Case Series: evaluating the clinical outcomes of 21 consecutive patients with metastatic thoracic and lumbar tumors after palliative surgery using PTA with posterior instrumentation. Surgery can offer patients pain relief and neurological improvements. It may also be cost effective. Neurological function can be maintained or improved by decompression and stabilization through a posterior approach as treatment for spinal metastases. The posterolateral transpedicular approach provides a wide surgical exposure to decompress and instrument the anterior and posterior spine. It avoids the morbidity associated with anterior approaches and provides immediate stability. Vascular tumors may be removed safely after embolization. Patients can be mobilized early after surgery. Neurological recovery, pain relief, and mobility can be enhanced by posterior decompression and stabilization in highly selective patients with spinal metastases. Posterior decompression, fixation, and fusion is a safe, efficacious method of treating selected patients with metastatic spine disease. This approach may be particularly useful in patients who cannot tolerate an anterior procedure, who have kyphosis, who harbor multiple spinal or extra-spinal or extra-spinal lesions, or whose tumor is predominantly dorsally located. Important improvement of function can be gained by surgical treatment, but the complication rate is high and many patients die of their disease within the first months of surgery. Even though lung cancer is considered an aggressive tumor, it is justifiable to aggressively treat patients with symptomatic spinal cord compression. Surgery by PTA can lead to good results in these patients. PTA with posterior instrumentation for metastatic thoracic and lumbar spinal tumors achieved good surgical results. Palliative surgery for patients with a Tomita's prognostic score of more than 8 may be considered in selected cases, especially in those with ECOG grade.