Classification and scoring systems for metastatic spine tumors: a literature review.

Introduction

The objective of treatment for metastatic spine tumors is to improve pain relief and anesthesia and to ensure maximum activities of daily living (ADL) and quality of life (QOL) in the short survival period. Actually, the symptoms and survival periods of patients with metastatic spine tumors vary widely, and sufficient consideration of the severity of symptoms and life prognosis is required for determining an effective therapeutic strategy. Accurate evaluation of metastasis and life prognosis before treatment is the most important factor in determining the therapeutic strategy for metastatic spine tumors.

However, we still lack an absolute evaluation method or prognostic factor. The tumor, lymph nodes, metastasis (TNM) classification is presently used as an index for primary malignant tumors, and similar indices are used internationally despite some variation among countries. As a result, a rough prognosis has been considered possible using the TNM classification in most cancers.

In spinal metastasis, predicting life expectancy is extremely important for the selection of a suitable therapeutic strategy, and the opinion of the attending physicians treating the primary lesion should be given top priority. However, the life expectancy predicted by them is not necessarily accurate, spinal metastasis itself is diverse, and uniform evaluation is impossible. Therefore, orthopedists and radiologists participating in the treatment have also evaluated spinal metastases and life prognoses from multidisciplinary viewpoints 1 , 2 ) . In the present study, we reviewed the representative classification and scoring systems reported to date.

Methods

A PubMed search was performed using the key words “classification” or “scoring” or “life expectancy” with “metastatic spine tumor” for the years from 1976 to 2016. The search using the keywords “classification” with “metastatic spine tumor” returned 140 articles.

Similarly, the search using the keywords “scoring” returned 67 articles and that using “life expectancy” in combination with metastatic spine tumor”. We reviewed most cited classifications and scorings before 2009, and did recent all classification and scorings which were reported after 2010.

Results

We performed acquisition of documents under former criteria, and reviewed six classifications and twenty-three scorings. Twenty-two of 23 scorings related to prediction of prognosis.

Classification/scoring of metastatic spine tumors: literature review

A. Anatomical classification

Historically, methods of evaluation according to the size and area of involvement of metastatic lesions have been proposed. Classification methods based on the location of the primary spinal tumor have been proposed by Enneking WF et al. (1980) 3 ) and McLain RF and Weinstein JN (1990); 4 ) however, they had shortcomings including challenges with differentiating some categories by images alone and the lack of consideration for spinal cord/nerve compression 1 ) . Boriani S et al. (1997) 5 ) proposed a clock type (transverse) classification of tumors according to their location by adding categorization of the dural tube ( Fig. 1 ). This classification method was excellent in that en bloc resection was always intended with preservation of the spinal cord in mind. For this reason, while the classification was useful in surgical planning for primary malignant tumors of the spine, it was not a reasonable method for the classification of spinal metastases, which were treated primarily by palliative decompression and fixation 1 ) .

Tomita K et al. (2001) 6 ) proposed a 7-category classification method mentioned above, which evaluated the sagittal involvement of the tumor in the transverse section alone adjusted to metastatic spine tumors ( Fig. 2 ). However, this classification was not necessarily useful, because the intracompartmental types 1 to 3 are clinically the same category and need not be classified for the selection of treatment 1 ) .

These anatomical classification methods are useful to an extent for the planning of surgery, but they are not necessarily correlated with the life prognosis. In addition, they are not decisive factors for the evaluation of surgical indications 1 ) .

With improvements in magnetic resonance imaging (MRI), it has become easy to evaluate transverse images of the spinal cord, and classification methods aimed to evaluate the severity of spinal cord compression have appeared. Bilsky MH et al. (2010) 7 ) classified the degree of compression of the dura mater and spinal cord at the site of maximum compression of the spinal cord by the tumor into 6 grades according to axial T2-weighted MR images ( Fig. 3 ). They also showed high inter- and intra-observer reliability of this classification. Although the classification has problems, such as the variation of the hardness and progression rate among tumors as well as urgency of spinal cord/nerve paralysis depending on the lesion level of the tumor, replication studies are anticipated, as there have been no classifications concerning spinal cord/nerve compression by tumors.

B. Classification or scoring system for neurological involvement and spinal instability

There are also classification methods based on neurological symptoms and spinal instability rather than the location of tumor. Harrington KD (1986) 8 ) proposed a simple 5-grade classification system taking spinal instability and neurological symptoms into consideration ( Table 1 ). Because surgery is clearly superior to radiotherapy as a treatment for metastatic spine tumors for the management of spinal instability, this classification method is useful in evaluating surgical indications for spinal metastasis. While it is theoretically excellent, it has limitations in concreteness and objectivity 1 ) . In addition, because of the lack of evaluation of the degree of neurological symptoms, paraplegia and radicular pain are classified in the same category. Therefore, it is difficult to predict life expectancy or functional outcome using this classification 1 ) . To compensate for such a lack of reliability and objectivity, the Spine Instability Neoplastic Score (SINS) 9 ) appeared as a new scoring system ( Table 2 ). According to the SINS consisting of 6 categories where the location of spinal metastasis, imaging findings, and pain were combined with a full score of 18, a higher score is considered to indicate more severe spinal instability. Because imaging findings do not necessarily correlate with clinical symptoms, the SINS, incorporating pain as a clinical symptom, is a clinically excellent scoring system. However, it has been reported that images are not easy to evaluate and that the kappa values of inter- or intra-observer agreement are not necessarily high. Therefore, caution must be exercised in the comparative evaluation of the score among examiners and hospitals 10 ) .

C. Scoring system for predicting life expectancy

1) Classic

Actually, the prognosis of metastatic spine tumor varies widely, and it is a major problem for the selection of treatment. Because general condition exerts a greater effect on prognosis than local condition, the evaluation of disease severity or prediction of outcome was difficult by imaging of the local condition. Therefore, Tokuhashi Y (1989, 1990) 11 , 12 ) devised a prognostic scoring system consisting of 6 items that are retrospectively considered to affect the outcome (general condition, Karnofsky performance 13 ) , number of bone metastases other than spine metastases, number of spine metastases, type of the primary lesion, presence or absence of metastasis to major organs, and state of paralysis) ( Table 3 ) 11 , 12 ) . Statistically, they retrospectively showed that the survival period was correlated with total score in 47 patients and predicted the outcome according to the prognostic criteria based on the total score. In the original version, the expected survival period was 3 months or less when the total score was 0-5, less than 12 months when the total score was 8 or higher, and 12 months or longer when the total score was 9 or higher. In the revised version of the prognostic criteria, in which primary lesions were scored 0-5 instead of 0-2 ( Table 4 ) 14 ) , the expected survival period was less than 6 months when the total score was 0-8, 6 months or longer when the total score was 9-11, and 1 year or longer when the total score was 12 or higher.

While statistical validation of these scoring systems is insufficient, the factors selected as affecting the survival period were relatively simple and easy to evaluate. In addition, they had no factors of therapeutic intervention, and the criteria were relatively flexible and versatile. Therefore, they have been evaluated by replication studies worldwide including our studies 15 , 16 ) , and relatively favorable results have been reported 2 , 17 - 19 ) .

These papers were the first reports on scoring systems for the prognosis of metastatic spine tumors and have long been landmark articles concerning the prognosis after the revision in 2005 14 ) . Similar scoring systems where factors related to the outcome are combined have been developed thereafter. In the same period, Yamashita et al. (1990) 20 ) also reported a staging system using bone scintigraphy for the prognosis of spinal metastasis. However, it was not accepted widely as the presence of metastasis to major organs exerted greater effects than the extent of bone metastasis evaluated by bone scintigraphy.

In the revised version of the Tokuhashi score 14 ) , the prognosis was classified into 3 categories with 6 months and 1 year, which are clinically key periods, as cut-off values. While the categorization by this system lacked precision, with the intermediate group partially overlapping the good prognosis group, it was applied inappropriately by rigidly defining scores of 9-11 as corresponding to a survival period of 6 months to 1 year 21 - 24 ) , and the agreement rate between the prognostic category and survival period was low in all these reports.

In addition, it has been suggested that the agreement rate between the survival period and score differs according to the type of the primary lesion and that the usefulness of the scoring system varies among cancer types. Yamashita T et al. (2011) 25 ) reported that the outcome was consistent with the prognostic category in 67 (79%) of the 85 patients followed-up for 1 year or longer. They also reported that the Tokuhashi score was useful irrespective of the treatment selected. However, while the low total score group showed a high correlation with poor outcome, the outcome was poor for the score concerning the kidney in many patients, and the kidney was suggested to be overweighted in scoring. In the same year, Hessler C et al. (2011) 26 ) maintained that the agreement rate between the revised Tokuhashi score and the actual survival period was 67.1% in a study of 76 patients who underwent surgery for spinal metastasis of lung cancer and that the scoring system was not adapted to recent advancements in the treatment of metastatic spine tumors. Some patients with spinal metastasis of lung cancer survive for 1 year or longer, and the outcome is relatively favorable in patients aged 50 years or less, those with metastasis to the lumbar spine, and those without paralysis. Tokuhashi et al. (2012) 27 ) basically agreed to this contention, admitting that the revised version had been prepared 13 years previously and that some patients with spinal metastases of lung cancer could survive for 2 years or longer as a result of advancements in treatment during this period. However, they refuted that the prognosis of spinal metastasis of lung cancer remained essentially poor and that the precision of the score should be evaluated by including patients for whom only conservative therapy was possible as well as surgically treated patients.

Some studies focused on the degree of differentiation among good prognosis, poor prognosis, and intermediate groups concerning the original and revised Tokuhashi score. Quraishi NA et al. (2013) 28 ) reported that 201 surgically treated patients could be differentiated into poor prognosis, moderate prognosis, and good prognosis groups with the predictive value between the actual and predicted survival of 64% or higher in all groups and 66% in all patients combined and that the scoring system was moderately useful. However, in 142 surgically treated patients reported by Pointillart V et al. (2011) 29 ) , the agreement rate between outcome and score was 60% or less according to both the original and revised versions.

There have also been studies that compared the original and revised versions. Wang M et al. (2012) 30 ) reported that the revised version of Tokuhashi score was particularly useful for metastases of prostate and breast cancers and that the original version was superior for the classification of metastases of colon cancer. They also observed that both versions were inadequate for metastases of lung and kidney cancers and that the overall precision was higher for the revised version than that for the original version. On the other hand, Liang T et al. (2013) 31 ) reported that the original version was more useful than the revised version or Tomita score (2001) 6 , 32 ) .

Tomita et al. (2001) 6 , 32 ) developed a new scoring system by retrospectively reviewing 67 patients including those treated conservatively ( Table 5 ).

Because items constituting the original Tokuhashi score were not differentially weighted, it was revised by weighting each factor of each item using the Cox proportional hazards model. It was simplified by excluding paralysis, which was not considered to affect the life prognosis. In addition, expected survival period and treatment selection including the indication for conservative therapy were specified in detail according to the total score: An expected survival period of 2 years or longer and en bloc excision for scores of 2-4, 1-2 years and debulking for scores of 4-6, 6-12 months and palliative decompression for scores of 6-8, and 3 months or less and terminal care for scores of 8-10.

This scoring system, prepared in a surgical patient-centered manner, is often used for the evaluation of surgical indications along with the Tokuhashi score, and its usefulness has been evaluated in many reports 2 , 33 - 40 ) .

Baur HCF (2002) 41 ) considered that this scoring system succeeded in the differentiation between poor and good prognosis groups but suggested underestimation of pain and paralysis, lack of specificity for urgent paralysis, and overemphasis of aggressive surgical treatments with understatement of indications for conservative therapy and palliative surgery. Baur HCF et al. (1995) 42 ) also developed a scoring system based on data from 153 patients with limb bone metastases and 88 patients with spinal involvements. They prepared a simple scoring system by combining 3 items identified as influential by Cox regression analysis after univariate analysis of prognostic factors, i.e., site of primary tumor, metastatic load, and pathological fracture ( Table 6 ). As a result, the 1-year survival rate was 0% in those having scores of 0-1, who all died within 6 months, 25% in those having scores of 2-3, and 50% in those having scores of 4-5. There were several limitations to this scoring system. It was difficult to evaluate the presence or absence of pathological fracture by imaging, and the scoring system was developed based on the data of a multicenter study in surgical cases alone with marked variation in surgical indications and procedures among the facilities.

van der Linden (2005) 43 ) devised a scoring system consisting of 3 items, i.e., Karnofsky performance status, type of the primary lesion (lung cancer, breast cancer, prostate cancer, others), and the presence or absence of metastasis to major organs, based on data from 342 patients with spinal metastases ( Table 7 ) and reported that the system was effective in 73% of the patients 43 ) .

Comparison of prognostic scoring systems was performed increasingly from around 2008. Leithner A et al. (2008) 44 ) and Wibmer C et al. (2011) 45 ) reported that, of the 7 scoring systems including the Tokuhashi score, Tomita score, and Linden score; those other than the Bauer scoring system were acceptable until 4 years after treatment. However, the Bauer score and modified Bauer score ( Table 8 ), in which the presence or absence of pathological fracture was excluded, were superior concerning the prognosis after 4 or more years and the differentiation between the good and moderate prognosis groups 44 , 45 ) . According to the modified Bauer scoring system, the median overall survival (OS) was 4.8 months. There was no surgical indication when the score was 0-1, the median OS was 18.3 months and posterior palliative surgery was indicated when the score was 2, and the median OS was 28.4 months and excisional surgery through antero-posterior combined approach was indicated when the score was 3-4. This group further conducted replication studies and reported that the modified Bauer system was superior to the other 6 systems 46 ) .

Chen H et al. (2010) 47 ) reported that the revised Tokuhashi score was practical and the most accurate in prognosis among 4 scoring systems, i.e., the revised Tokuhashi score 14 ) , Tomita score 6 ) , Bauer score 42 ) , and revised van der Linden score 43 ) , in 41 patients with spinal metastases of hepatocellular carcinoma. Moreover, they proposed the serum albumin and lactate dehydrogenase (LDH) levels as useful prognostic factors.

In addition, in the field of radiology, Rades D et al. (2008) 48 ) prepared a few scoring systems retrospectively using data obtained from patients who underwent radiotherapy for spinal cord compression by metastatic tumors. The scoring system was developed from 1,852 cases of spinal metastasis ( Table 9 ) 48 ) , and they reported the results of its prospective application to 439 subsequent cases (2010, Table 9 ) 49 ) . They also prepared a scoring system for different cancer types. In addition to scoring systems for metastases of prostate cancer (2012) 50 ) and metastases of breast cancer (2013) 51 ) , a scoring system for unknown primary tumors has been developed by Douglas et al. (2013) 52 ) .

In all these scoring systems, conditions for which radiotherapy (RT) is indicated for spinal cord compression in the advanced stage of metastatic tumors are evaluated. Moreover, other bone metastases at the time of RT, visceral metastases at the time of RT, interval from tumor diagnosis to metastatic spinal cord compression (MSCC), ambulatory status before RT, and time of developing motor deficits before RT are selected as factors, and the combination of items and score allocations are modified according to the cancer type. It is important to mention that application of these scoring systems is limited to advanced stages of cancer with spinal metastases and impending paralysis, and that a single pattern is not applied to different cancer types. Because treatment is limited to radiotherapy, scoring systems are not adapted to the recent diversified treatment selections 2 ) .

The Katagiri score (2005) 53 ) is a scoring system incorporating therapeutic intervention. It was derived retrospectively from 350 cases of skeletal metastases and is characterized by the inclusion of chemotherapy history before the onset of spinal metastasis. Initially, the extent of intervention by chemotherapy, individual differences, and sensitivity were evaluated vaguely, and the system had major limitations concerning versatility and objectivity. However, as the survival period of patients has been prolonged recently owing to improvements in adjuvant therapies, such as molecularly targeted drugs, the history of chemotherapy has become an important prognostic factor. Katagiri et al. also reported a new scoring system with modifications of score allocation for breast and prostate cancers according to hormone dependence or independence of the primary lesions and for lung cancer according to the use or non use of molecular targeted drugs and incorporation of laboratory data ( Table 10 , 2014) 54 ) . In a series of 808 patients, the 2-year survival rate was reported to be 77.8% in a group with a total score of 0-3, the 1-year survival rate was 49.3%, and the 6-month survival rate was 74.0%, in a group with a total score of 4-6, and the 6-month survival rate was 26.9% in a group with a total score of 7-10.

2) Significance and problems

All these prognostic scoring systems were prepared by combining factors that affect the outcome 2 ) . We found 22 scoring systems by searching the PubMed after the Tokuhashi score until 2016 6 , 11 , 12 , 14 , 42 - 45 , 48 - 64 ) . The type of the primary lesion was the only prognostic factor adopted in all these scoring systems, and the other factors affecting prognosis were selected differently. Following the type of primary lesion, metastasis to major organs, general condition (performance status), and the number of bone metastases were selected most frequently ( Fig. 4 ).

Rades et al. attached importance to functional factors and reported a scoring system with emphasis on the ambulation ability before treatment and rate of progression of paralysis as prognostic factors 47 - 51 , 54 ) , but many scoring systems including the one by Tomita completely disregarded paralysis 6 , 42 - 45 ) . This variation is considered to be explained by the differences in the characteristics of patients evaluated for their preparation. All patients evaluated by Rades et al. had progressive spinal cord paralysis and underwent radiotherapy, and included a considerable number of patients with poor prognoses having no indications for surgery. Therefore, the outcomes of their patients were considerably poorer compared with those of the patients used for the preparation of other scoring systems 2 ) .

Recent reviews have suggested 1) the function status, 2) number of visceral metastases, and 3) primary tumor pathology as factors that exert the greatest effects on outcome 65 - 67 ) . Moreover, presently, treatment for metastasis is initiated as soon as asymptomatic metastasis is detected. Kawai T et al. (2013) reported that prognostic factors should be reevaluated, because the timing of therapeutic intervention has changed from before 68 ) . In fact, the occurrence and progression of bone metastasis are suppressed by the administration of bisphosphonates and anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, and it is necessary to evaluate prognostic factors in consideration of the sensitivity to these bone-modifying agents (BMA).

At any rate, such additive scoring systems combining factors that affect the outcome are undoubtedly useful for the general prognosis at present, because there is no single absolute prognostic factor 2 , 69 ) . However, no scoring system has been reported to have achieved a consistency rate of 90% or higher between the expected and actual survival periods on prospective analysis 2 ) . Therefore, which of the scoring systems is optimal remains uncertain.

There have been few reports on replication studies on the precision of prognostic scoring systems other than the Tokuhashi score and the subsequent Tomita score. Even the revised version of the Tokuhashi score was prepared more than 20 years previously and has become outdated in view of the prolonged survival state owing to advancements in treatments 63 , 64 ) .

These scoring systems have been used for predicting life expectancy and selection of treatments 65 ) , but they are also used to avoid overtreatment in patients with poor prognoses. Rades D et al. (2013) 56 ) evaluated risk factors of death within 2 months after radiotherapy and reported that mortality within 2 months was 96.0% with a specificity of 99.8% when the score was 24 or higher ( Table 11 ).

There are also objections to limiting treatment options on the basis of a simple mathematical index provided by such a scoring system 70 - 72 ) . Gasbarrini A et al. 70 , 71 ) stressed the importance of evaluation of individual patients in particular consideration of their sensitivity to adjuvant therapies and proposed a treatment algorithm emphasizing multidisciplinary treatment selection incorporating a scoring system. Paton GR et al. 73 ) also proposed a therapeutic strategy in consideration of the tumor location level (L), mechanical instability (M), neurology (N), oncology (O), patient fitness, prognosis, and prior therapy (P).

Moreover, as functional prognosis depends on the survival period because of the nature of disease, these scoring systems are also used for predicting functional outcomes. Tang V et al. (2007) 74 ) used the Tokuhashi score to evaluate the indications for inpatient rehabilitation, because the score is correlated with the Functional Independence Measure (FIM) after rehabilitation. In addition, Yamashita T et al. (2008) 75 ) and Putz C et al. (2008) 76 ) reported that the Tokuhashi score can also be used for the prediction of functional recovery as it is correlated with neurological recovery. Rades D et al. also reported that walking ability after treatment could be predicted from survival factors of prognostic scores 77 ) .

3) Future

As for the future of scoring systems, it is considered necessary to primarily adopt more oncological viewpoints, which are lacing in conventional scoring systems. Such viewpoints include 1) consideration of the stage and height of lesions, 2) evaluation of individual primary lesions, 3) addition of serum laboratory items as prognostic factors, and 4) consideration of multidisciplinary treatment, etc.

Concerning the stage of the disease, with advancements in the ability to detect metastases, features of metastatic spine tumors have been shown to change from the stage of progressive spinal cord paralysis and terminal stage to the asymptomatic stage, and it has become impossible to apply a single scoring system to all these stages. Scoring systems should be prepared and applied at least by clarifying the stage for which they are intended. Concerning the level of the lesion, it has been asserted that there is no appropriate scoring system for the cervical spine, which is an infrequent site of metastasis 78 ) .

Regarding the evaluation of individual primary lesions, marked improvements in the prognosis of spinal metastasis have been observed owing to the rapid development of treatments in some cancers, and many authors have suggested that improvements in prognosis should be reflected in scoring systems 25 , 79 ) . The necessity of scoring systems for specific cancer types has been maintained from before 80 - 82 ) , and scoring systems for specific types of cancer are expected to be increasingly prepared with accumulation of cases and systematization of treatments. For some cancer types, it is sufficiently possible to adopt specific tumor markers, etc., as prognostic factors. Crnalic S et al. 55 ) reported a scoring system for prostate cancer incorporating the prostate-specific antigen ( Table 12 ) 55 ) .

In addition, consideration of multidisciplinary treatments is required. Gregory TM et al. proposed that prognostic scoring systems should be changed by introducing anti-vascular endothelial growth factor (VEGF) 83 ) . In the Lei score (2016) 64 ) , which was reported recently, categorization of primary lesions by the Katagiri new score was adopted, the score allotment was changed for breast and prostate cancers depending on whether they are hormone-dependent or independent and for lung cancer depending on whether molecularly targeted drugs are used or not, and the history of chemotherapy was adopted as a prognostic factor.

Conclusion

These classification, evaluation, and scoring systems have been generally useful in the selection of suitable treatment strategies. However, we emphasize the necessity of multidisciplinary development and revision of classification and evaluation methods to adapt to the prolongation of survival associated with increased diversity and advancements of treatments.

Conflicts of Interest: The authors declare that there are no conflicts of interest.

1. Choi D, Crockard A, Bunger C, et al. Review of metastatic spine tumour classification and indications for surgery: the consensus statement of the Global Spine Tumour Study Group. Eur Spine J 2010; 19(2): 215-222. 10.1007/s00586-009-1252-x PMC2899817 20039084

2. Tokuhashi Y, Uei H, Oshima M, et al. Scoring system for prediction of metastatic spine tumor prognosis. World J Orthop 2014; 5(3): 262-271. 10.5312/wjo.v5.i3.262 PMC4095019 25035829

3. Enneking WF, Spainer SS, Goodman MA. A system for the surgical staging of musculosketetal sarcoma. Clin Orthop 1980; 153: 106-120. 7449206

4. Robert F, McLain RF, Weinstein JN. Tumors of the spine. Semin Spine Surg 1990; 2(3): 157-180.

5. Boriani S, Weinstein JN, Biagini R. Primary bone tumors of the spine: terminology and surgical staging. Spine 1997; 22(9): 1036-1044. 10.1097/00007632-199705010-00020 9152458

6. Tomita K, Kawahara N, Kobayashi T, et al. Surgical strategy for spinal metastases. Spine 2001; 26(3): 298-306. 10.1097/00007632-200102010-00016 11224867

7. Bilsky MH, Laufer I, Fourney DR, et al. Reliability analysis of the epidural spinal cord compression scale. J Neurosurg Spine 2010; 13(3): 324-328. 10.3171/2010.3.SPINE09459 20809724

8. Harrington KD. Metastatic disease of the spine. J Bone Joint Surg 1986; 68A(7): 110-1115. 3745256

9. Fisher CG, Dipaola CP, Ryken TC, et al. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 2010; 35(22): E1221-E1229. 10.1097/BRS.0b013e3181e16ae2 20562730

10. Arana E, Kovacs FM, Royuea A, et al. Spine instability neoplastic score: agreement across different medical and surgical specialties. Spine J 2016; 16(5): 591-599. 10.1016/j.spinee.2015.10.006 26471708

11. Tokuhashi Y, Kawano H, Ohsaka S, et al. A scoring system for preoperative evaluation of the prognosis of metastatic spine tumor (a preliminary report). Nihon Seikeigeka Gakkai Zasshi 1989; 63(5): 482-489 (in Japanese). 2794626

12. Tokuhashi Y, Matsuzaki H, Toriyama S, et al. Scoring system for the preoperative evaluation of metastatic spine tumor prognosis. Spine 1990; 15(11): 1110-1113. 10.1097/00007632-199011010-00005 1702559

13. Karnofsky DA. Clinical evaluation of anticancer drugs: Cancer chemotherapy. GANN Monograph 1967; 2: 223-231.

14. Tokuhashi Y, Matsuzaki H, Oda H, et al. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine 2005; 30(19): 2186-2191 [PMID: 16205345] 10.1097/01.brs.0000180401.06919.a5 16205345

15. Tokuhashi Y, Matsuzaki H, Kawano H, et al. [The indication of operative procedure for a metastatic spine tumor: a scoring system for the preoperative evaluation of the prognosis]. Nihon Seikeigeka Gakkai Zasshi 1994; 68(5): 379-389. (in Japanese) 8051465

16. Tokuhashi Y, Ajiro Y, Umezawa N. Outcome of treatment for spinal metastases using scoring system for preoperative evaluation of prognosis. Spine 2009; 34(1): 69-73. 10.1097/BRS.0b013e3181913f19 19127163

17. Enkaua EA, Doursounian L, Chatellier G, et al. Vertebral metastases, a critical appreciation of the preoperative prognostic Tokuhashi score in a series of 71 cases. Spine 1997; 22(19): 2293-2298. 10.1097/00007632-199710010-00020 9346151

18. Riegel T, Schilling T, Sitter H, et al. Analysis of factors affecting the prognosis of vertebral metastases. Zentralbl Neurochir 2002; 63(1): 2-6. 10.1055/s-2002-31578 12098076

19. Ulmar B, Richter M, Cakir B, et al. The Tokuhashi score: significant predictive value for the life expectancy of patients with breast cancer with spinal metastases. Spine 2005; 30(19): 2222-2226. 10.1097/01.brs.0000181055.10977.5b 16205351

20. Yamashita K, Ueda T, Komatsubara Y, et al. Breast cancer with bone- only metastases: visceral metastases-free rate in relation to anatomic distribution of bone metastases. Cancer 1991; 68(3): 634-637. 10.1002/1097-0142(19910801)68:3<634::aid-cncr2820680332>3.0.co;2-b 2065284

21. Majeed H, Kumar S, Bommireddy R, et al. Accuracy of prognostic scores in decision making and predicting outcomes in metastatic spine disease. Ann R Coll Surg Engl 2012; 94(1): 28-33. 10.1308/003588412X13171221498424 PMC3954183 22524919

22. Hernandez-Fernandez A, Vélez R, Lersundi-Artamendi A, et al. External validity of the Tokuhashi score in patients with vertebral metastasis. J Cancer Res Clin Oncol. 2012; 138(9): 1493-1500. 10.1007/s00432-012-1222-2 PMC11824288 22526160

23. Padalkar P, Tow B. Predictors of survival in surgically treated patients of spinal metastasis. Indian J Orthop 2011; 45(4): 307-313. 10.4103/0019-5413.82333 PMC3134014 21772622

24. Tabouret E, Cauvin C, Fuentes S, et al. Reassessment of scoring systems and prognostic factors for metastatic spinal cord compression. Spine J 2013; 15(5): 944-950. 10.1016/j.spinee.2013.06.036 24120144

25. Yamashita T, Siemionow KB, Mroz T, et al. A prospective analysis of prognostic factors in patients with spinal metastases: Use of the revised Tokuhashi score. Spine 2011; 36(11): 910-917. 10.1097/BRS.0b013e3181e56ec1 21037529

26. Hessler C, Vettorazzi E, Madert J, et al. Actual and predicted survival time of patients with spinal metastases of lung cancer: evaluation of the robustness of the Tokuhashi score. Spine 2011; 36(12): 983-989. 10.1097/BRS.0b013e3181e8f7f8 21217434

27. Tokuhashi Y, Oshima M, Uei H. Letter to editor. Spine 2012; 37(5): 429. 10.1097/BRS.0b013e31824589be 22198349

28. Quraishi NA, Manoharan SR, Arealis G, et al. Accuracy of the revised Tokuhashi score in predicting survival in patients with metastatic spinal cord compression (MSCC). Eur Spine J 2013; 22 Suppl 1: S21-S26. 10.1007/s00586-012-2649-5 PMC3578515 23328875

29. Pointillart V, Vital JM, Salmi R, et al. Survival prognostic factors and clinical outcomes in patients with spinal metastases. J Cancer Res Clin Oncol 2011; 137(5): 849-856. 10.1007/s00432-010-0946-0 PMC11827924 20820803

30. Wang M, Bünger CE, Li H, et al. Predictive value of Tokuhashi scoring systems in spinal metastases, focusing on various primary tumor groups: evaluation of 448 patients in the Aarhus spinal metastases database. Spine 2012; 37(7): 573-582. 10.1097/BRS.0b013e31822bd6b0 21796024

31. Liang T, Wan Y, Zou X, et al. Is surgery for spine metastasis reasonable in patients older than 60 years? Clin Orthop Relat Res 2013; 471: 628-639. 10.1007/s11999-012-2699-3 PMC3549148 23179121

32. Kawahara N, Tomita K, Murakami H, et al. Total en bloc spondylectomy for spinal tumors: surgical techniques and related basic background. Orthop Clin North Am 2009; 40(1): 47-63. 10.1016/j.ocl.2008.09.004 19064055

33. Zairi F, Arikat A, Allaoui M, et al. Minimally invasive decompression and stabilization for the management of thoracolumbar spine metastasis. J Neurosurg Spine 2012; 17(1): 19-23. 10.3171/2012.4.SPINE111108 22607222

34. Walter J, Reichart R, Waschke A, et al. Palliative considerations in the surgical treatment of spinal metastases: evaluation of posterolateral decompression combined with posterior instrumentation. J Cancer Res Clin Oncol 2012; 138(2): 301-310. 10.1007/s00432-011-1100-3 PMC11824806 22127369

35. Zhang D, Xu W, Liu T, et al. Surgery and prognostic factors of patients with epidural spinal cord compression caused by hepatocellular carcinoma metastases. Spine 2013; 38(17): E1090-E1095. 10.1097/BRS.0b013e3182983bf8 23632333

36. Cho DC, Sung JK. Palliative surgery for metastatic thoracic and lumbar tumors using posterolateral transpedicular approach with posterior instrumentation. Surg Neurol 2009; 71(4): 424-433. 10.1016/j.surneu.2008.02.049 18586305

37. Omeis I, Bekelis K, Gregory A, et al. The use of expandable cages in patients undergoing multilevel corpectomies for metastatic tumors in the cervical spine. Orthopedics 2010; 33(2): 87-92. 10.3928/01477447-20100104-12 20192145

38. Sundaresan N, Rothman A, Manhart K, et al. Surgery for solitary metastases of the spine: rationale and results of treatment. Spine 2002; 27(16): 1802-1806. 10.1097/00007632-200208150-00021 12195075

39. Chi JH, Gokaslan Z, McCormick P, et al. Selecting treatment for patients with malignant epidural spinal cord compression-does age matter?: results from a randomized clinical trial. Spine 2009; 34(5): 431-435. 10.1097/BRS.0b013e318193a25b 19212272

40. Hu Y, Xia Q, Ji J, et al. One-stage combined posterior and anterior approaches for excising thoracolumbar and lumbar tumors: surgical and oncological outcomes. Spine 2010; 35(5): 590-595. 10.1097/BRS.0b013e3181b967ca 20118840

41. Bauer H. Surgical Strategy for spinal metastases. Spine 2002; 27(10): 1124-1125. 10.1097/00007632-200205150-00027 12004183

42. Bauer H, Wedin R. Survival after surgery for spinal and extremity metastases. Prognostication in 241 patients. Acta Orthop Scand 1995; 66(2): 143-146. 10.3109/17453679508995508 7740944

43. van der Linden YM, Dijkstra SP, Vonk EJ, et al. Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. Cancer 2005; 103(2): 320-328. 10.1002/cncr.20756 15593360

44. Leithner A, Radl R, Gruber G, et al. Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur Spine J 2008; 17(11): 1488-1495. 10.1007/s00586-008-0763-1 PMC2583181 18787846

45. Wibmer C, Leithner A, Hofmann G, et al. Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems. Spine 2011; 36(23):1977-1986. 10.1097/BRS.0b013e3182011f84 21304424

46. Dardic M, Wibmer C, Berghold A, et al. Evaluation of prognostic scoring system for spinal metastases in 196 patients treated during 2005-2010. Eur Spine J 2015; 24(10): 2133-2141. 10.1007/s00586-014-3482-9 25082760

47. Chen H, Xiao J, Yang X, et al. Preoperative scoring systems and prognostic factors for patients with spinal metastases from hepatocellular carcinoma. Spine 2010; 35(23): E1339-E1346. 10.1097/BRS.0b013e3181e574f5 20938387

48. Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer 2008; 112(1): 157-161. 10.1002/cncr.23150 17948910

49. Rades D, Douglas S, Veninga T, et al. Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression. Cancer 2010; 116(15): 3670-3673. 10.1002/cncr.25223 20564129

50. Rades D, Douglas S, Veninga T, et al. A survival score for patients with metastatic spinal cord compression from prostate cancer. Strahlenther Onkol 2012; 188(9): 802-806. 10.1007/s00066-012-0106-3 22526228

51. Rades D, Douglas S, Schild SE. A validated survival score for breast cancer patients with metastatic spinal cord compression. Strahlenther Onkol 2013; 189(1): 41-46. 10.1007/s00066-012-0230-0 23138773

52. Douglas S, Schild SE, Rades D. Metastatic spinal cord compression in patients with cancer of unknown primary. Estimating the survival prognosis with a validated score. Strahlenther Onkol 2012; 188(11): 1048-1051. 10.1007/s00066-012-0130-3 23053138

53. Katagiri H, Takahashi M, Wakai K, et al. Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br 2005; 87(5): 698-703. 10.1302/0301-620X.87B5.15185 15855375

54. Katagiri H, Okada R, Takagi T, et al. New Prognostic factors and scoring system for patients with skeletal metastasis. Cancer Medicine 2014; 3(5): 1359-1367. 10.1002/cam4.292 PMC4302686 25044999

55. Sioutos PJ, Arbit E, Meshulam CF, et al. Spinal metastases from solid tumors. Analysis of factors affecting survival. Cancer 1995; 76(8): 1453-1459. 10.1002/1097-0142(19951015)76:8<1453::aid-cncr2820760824>3.0.co;2-t 8620423

56. Rades D, Hueppe M, Schild SE. A score to identify patients with metastatic spinal cord compression who may be candidates for best supportive care. Cancer 2013; 119(4): 897-903. 10.1002/cncr.27849 23065671

57. Crnalic S, Löfvenberg R, Bergh A, et al. Predicting survival for surgery of metastatic spinal cord compression in prostate cancer: a new score. Spine 2012; 37(26): 2168-2176. 10.1097/BRS.0b013e31826011bc 22648028

58. North RB, LaRocca VR, Schwartz J, et al. Surgical management of spinal metastases: analysis of prognostic factors during a 10-year experience. J Neurosurg: Spine 2005; 2(5): 564-573. 10.3171/spi.2005.2.5.0564 15945430

59. Balain B, Jaiswal A, Trivedi JM, et al. The Oswestry Risk Index: an aid in the treatment of metastatic disease of the spine. Bone Joint J 2013; 95-B(2): 210-216. 10.1302/0301-620X.95B2.29323 23365031

60. Bakker NA, Coppes MH, Vergeer RA, et al. Surgery on spinal epidural metastases (SEM) in renal cell carcinoma: a plea for a new paradigm. Spine J 2014; 14(9): 2038-2041. 10.1016/j.spinee.2014.04.013 24768747

61. Bollen L, van der Linden YM, Pondaag W, et al. Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1,043 patients. Neuro Oncol 2014; 16(7): 991-998. 10.1093/neuonc/not318 PMC4057139 24470544

62. Ghori AK, Leonard DA, Schoenfeld AJ, et al. Modeling 1-year survival after surgery on the metastatic spine. Spine J 2015; 15(11): 2345-2350. 10.1016/j.spinee.2015.06.061 26160329

63. Lei M, Liu Y, Yan L, et al. A validated preoperative score predicting survival and functional outcome in lung cancer patients operated with posterior decompression and stabilization for metastatic spinal cord compression. Eur Spine J 2015; 25: 3971-3978. 10.1007/s00586-015-4290-6 26507323

64. Lei M, Li J, Liu Y, et al. Who are the best candidates for decompressive surgery and spine stabilization in patients with metastatic spinal cord compression? A new scoring system. Spine 2016; 41(18): 1469-1476. 10.1097/BRS.0000000000001538 PMC5001136 26937605

65. Switlyk MD, Kongsgaard U, Skejeldal S, et al. Prognostic factors in patients with symptomatic spinal metastases and normal neurological function. Clinical Oncology 2015; 27(4): 213-221. 10.1016/j.clon.2015.01.002 25624156

66. Sharf S, Qadeer M. Metastatic spine: A review. WScJ 2016; 1(1): 58-63.

67. Oliveira MF, Rotta JM, Botelho RV. Survival analysis in patients with metastatic spinal disease: the influence of surgery, histology, clinical and neurologic status. Arq Neuropsiquiatr 2015; 73(4): 330-335. 10.1590/0004-282X20150003 25992524

68. Kawai T, Aota Y, Yamashita T, et al. Analysis of survival prognostic factors in patients with newly detected metastatic spinal tumors. J Spine Res 2013; 4(1): 136-142.

69. Tokuhashi Y, Ajiro Y, Oshima M. Algorithm and planning in metastatic spine tumors. Orthop Clin North Am 2009; 40(1): 37-46. 10.1016/j.ocl.2008.09.002 19064054

70. Gasbarrini A, Cappuccio M, Mirabile L, et al. Spinal metastases treatment evaluation algorithm. ERMP 2004; 8(6): 265-274. 15745386

71. Gasbarrini A, Li H, Cappuccio M, Mirabile L, et al. Efficacy evaluation of a new treatment algorithm for spinal metastases. Spine 2010; 35(15): 1466-1470 10.1097/BRS.0b013e3181c680b9 20195197

72. Sun YQ, Cai YB, Rong GW. [Comparison of evaluating system for patients with spinal metastases]. Zhonghua Wai Ke Za Zhi 2003; 41(8): 570-574 (in Chinese). 14505527

73. Paton GR, Frangou E, Fourney DR. Contemporary treatment strategy for spinal metastasis: the "LMNOP" system. Can J Neurol Sci 2011; 38(3): 396-403. 10.1017/s031716710001177x 21515496

74. Tang V, Harvey D, Park Dorsay J, et al. Prognostic indicators in metastatic spinal cord compression: using functional independence measure and Tokuhashi scale to optimize rehabilitation planning. Spinal Cord 2007; 45(10): 671-677. 10.1038/sj.sc.3102024 17228353

75. Yamashita T, Aota Y, Kushida K, et al. Changes in physical function after palliative surgery for metastatic spinal tumor: association of the revised Tokuhashi score with neurologic recovery. Spine 2008; 33(21): 2341-2346. 10.1097/BRS.0b013e3181878733 18827700

76. Putz C, Wiedenhöfer B, Gerner HJ, et al. Tokuhashi prognosis score: an important tool in prediction of the neurological outcome in metastatic spinal cord compression: a retrospective clinical study. Spine 2008 15; 33(24): 2669-2674 10.1097/BRS.0b013e318188b98f 18981960

77. Rades D, Rudat V, Veninga T, et al. A score predicting posttreatment ambulatory status in patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 2008; 72(3): 905-908. 10.1016/j.ijrobp.2008.02.018 18436390

78. Cho W, Chang UK. Neurological and survival outcomes after surgical management of subaxial cervical spine metastases. Spine 2012; 37(16): E969-E977 10.1097/BRS.0b013e31824ee1c2 22343276

79. Morgen SS, Lund-Andersen C, Larsen CF, et al. Prognosis in patients with symptomatic metastatic spinal cord compression: survival in different cancer diagnosis in a cohort of 2321 patients. Spine 2013; 38(16): 1362-1367. 10.1097/BRS.0b013e318294835b 23574811

80. Ogihara S, Seichi A, Hozumi T, et al. Prognostic factors for patients with spinal metastases from lung cancer. Spine 2006; 31(14):1585-1590. 10.1097/01.brs.0000222146.91398.c9 16778693

81. Shehadi JA, Sciubba DM, Suk I, et al. Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients. Eur Spine J 2007; 16(8): 1179-1192. 10.1007/s00586-007-0357-3 PMC2200772 17406908

82. Williams BJ, Fox BD, Sciubba DM, et al. Surgical management of prostate cancer metastatic to the spine. J Neurosurg Spine 2009; 10(5): 414-422. 10.3171/2009.1.SPINE08509 19442002

83. Gregory TM, Coriat R, Mir O. Prognostic scoring systems for spinal metastases in the era of anti-VEGF therapies. Spine 2013; 38(11): 965-966 10.1097/BRS.0b013e3182609d38 22648032