METASTASIS: DIAGNOSIS, TREATMENT AND PROGNOSIS INTEGRATIVE REVIEW FROM 2012 TO 2017

Care of the patient with spinal metastasis is challenging. The topic of this article is the treatment and prognosis of spinal metastases, aiming to enumerate and analyze literature that addresses this treatment and prognosis. The methodology used was an integrative review in the Virtual Health Library. Nineteen articles were identified demonstrating that there is research and scientific production in this area. The thematic units and their categories are: treatment decision - prognostic scales or clinical neurological evaluation; types of treatment - minimally invasive and/or traditional; and effectiveness of prognostic scales higher or lower probability of success, which provide insight into the different possibilities of patient evaluation and their applicability in practice. When making the diagnosis, planning the treatment, and establishing a prognosis, the professional must be in sync with current precepts and act based on the objective and subjective characteristics of the patients, such as beliefs and values, which although immeasurable, influence the survival and the effectiveness of treatment. Level of evidence I; Integrative Review.


INTRODUCTION METHODS
This is an integrative review of the Virtual Health Library (VHL), a Brazilian database with recognized reliability and free access, with inclusion criteria using neoplasm metastasis, spine, therapy, prognosis, in the health science descriptors, in the period from 2012 to 2017, in Portuguese, English and Spanish. The exclusion criteria were inability to access, duplicate publications, other languages, outside of the timeframes, and articles not related to the theme. The Impact Factor (IF) of the literature found, as well as the Level of Evidence (LE) and the Degree of Recommendation (DR) of each article according to the classification of the Centre for Evidence-Based Medicine (CEBM) in the United Kingdom, were included in the analysis. [13][14][15][16][17]

RESULTS
The initial literature total was 178 articles, of which 19 remained after selection. (Table 1) The 19 articles are from globally recognized periodicals with a predominance of original (74%), research (10%), review (10%), and experience report (6%) articles. There was a relative predominance of foreign periodicals (58%) and the databases were MEDLINE -Online Medical Literature Research and Analysis System of the National Library of Medicine of the United States of America (58%) and LILACS-Latin American and Caribbean Health Sciences Literature database (42%). The predominant IF value was less than 1 in 60% of the literature, from 1 to 2.99 in 30% of the literature, and from 3 to 4.9 in 10% of the literature as shown in Table 2.
The validation of these articles is described in Table 3. The thematic units and categories found are described in Table 4.

DISCUSSION
Analyzing the 19 articles found in the 2012 to 2017 timeframe, it was verified that scientific production about the treatment and prognosis of spinal metastases continued during those years, although there were no publications from 2017, perhaps because at the time of the study it was only the beginning of 2018.
The fact that the articles were included in recognized periodicals makes it possible to infer that there is a real concern for spinal metastases among professionals, as most of the periodicals represent medical societies from different countries dedicated to this area, and these periodicals constitute a space for the promotion of scientific and technical knowledge, and the incentive and investment in scientific and operational research towards continuous healthcare quality improvement must be constant. [36][37][38][39] The predominance of original articles in the literature, followed by the publication of research, literature reviews, and experience reports confirms the investment of professionals in the analysis of spinal metastases, principally in the area of treatment and prognosis, in search of new alternatives that build new foundations for actions in the field of spinal metastases. In this sense, communication and dissemination are essential to scientific progress and they confer legitimacy and recognition for the development of tools and the implementation of competences. 40 Most of the authors are neurosurgeons, some are professors and two are medical resident authors in this area, as well as radiotherapists and orthopedists, highlighting their concern with the growth and specificity of this area of medicine, which requires trained human resources committed to permanent education. 41,42 In this sense, it is worth noting that medical specialties are more than a simple division of labor. They result from medical development, scientific progress, and the deepening of knowledge and they are fundamental for patient needs in clinical situations that demand technical capacity, in the intelligence and specific skills of the physician, and, in the case of spinal metastasis, multi-professional work is essential for accurate decision-making. [43][44][45] The IF of the selected articles shows that all the periodicals are indexed at the Institute for Scientific Information (ISI), published in the Journal Citation Reports (JCR) and in Thomson Reuters, and are therefore recognized and published internationally. Although 60% have an IF score of less than 1, it is important to note that IF is the most used bibliometric indicator at the international level. It receives criticism, since there is the possibility that scientific journals try to manipulate this impact factor through the incorporation of a greater number of systematic review articles, more cited than the others, or encouraging self-citations, in addition to the fact that there is generally a higher search rate for articles written in English, which may explain the lower IF of Brazilian publications. 46 The literature found in the MEDLINE and LILACS databases has credibility because these sources are leaders in the areas of health and medicine and both provide bodies of data that are interrelated, that perpetuate dissemination, and that represent updated, reliable publications from the scientific community. 47 Regarding the methodology of the articles, most involve reproducible, prospective or retrospective cohort studies, aiming to enable the reproduction of any reported phenomenon, a quality essential for scientific status, as well as studies of case series, reviews, and case and experience reports, which add benefits to current practices or suggest new directions by sharpening the interpretation of knowledge and learning. 48,49 Regarding the Degree of Recommendation of the articles selected, with Grade A -26%, Grade B -69%, and Grade D -5%, the achievement of Grade A or B by most of them indicates that these articles have rigorous scientific proof to guide decision making,   To validate the available survival forecasting tools in a group of patients submitted to reirradiation of spinal metastases in a single institution

Case Series
The estimate of reirradiation survival used by the radio-oncologist: primary tumor, central nervous system metastases, and general metastatic load -little efficacy compared to SPT-Nieder that uses the KPS-Karnofsky Performance Status index, liver metastases and steroid use. SPT-Nieder higher prognostic precision, but the item pleural effusion was not correlated in the study. To find out about therapeutic modalities in spinal metastasis Literature Review Treatment of spinal metastasis should be individualized and multidisciplinary: neurosurgeons, oncologists, oncologic surgeons, radiotherapists, physiatrists, pain specialists, psychologist among others.
The rational choice of the therapeutic modality should be based on the clinical and neurological condition of the patient, life expectancy, degree of spinal impairment, histological type of the neoplasia, and desire of the patient and the family.

3A B
Evaluation of the interobserver reproducibility of a new scale for orientation of therapeutic conduct in spinal metastases: SINS score (Spine Instability Neoplastic Score) 25 To evaluate the impact on conduct and quantify the interobserver reproducibility of the SINS score. In addition, to determine its applicability in our environment.

Retrospective reproducibility study
The SINS is applicable in Brazil. Divergence between the evaluations in terms of the stability of lesions before and after the application of SINS. However, the therapeutic conduct was not modified for this new score. The SINS has moderate interobserver reproducibility.
1A A Current paradigms for metastatic medullary disease: an evidencebased review 26 To review decision-making strategies that determine the most effective treatment options.

Evidence-based review
Surgical oncology developing change in the management of surgical patients with metastatic tumors. Greater vision: tumor biology, of the surgical approaches, oncology by radiation instrumentation, stereotactic radiosurgery, and intensity-modulated radiation therapy To analyze surgery of metastases, arthrodesis / pedicle screws via isolated posterior approach.
Retrospective / case series Surgery through arthrodesis / pedicular instrumentation / decompression brings significant clinical benefits, improved pain and neurological profiles.

3B B
summarizing the research available on the treatment and prognosis of spinal metastasis. The only article with Recommendation Grade D deals with a bold proposal yet untested in humans and equally important to the production of knowledge. 50,51 The categories "prognostic scales and/or clinical evaluation scales" in the "treatment decision" thematic unit highlight that professionals should ally the scales with the institutional resources, the professional experience, and above all with the holistic view of the patient, with their acquiescence to treatment and the tangible benefits of that treatment for the patients. This finding agrees with other scholars who affirm that treatment should not be based solely on scales, but also on the individual characteristics of each patient. 52,53 The scales discussed in the articles selected are the KPS classification, the original or adapted scores of Frankel, Harrington, Tomita, Tokuhashi, Bauer, Chow, Enneking, ECOG, the criteria of Panjabi et al., the criteria of Kostuik, the spinal instability neoplastic score (SINS), the LANSS pain scale and/or the visual analog scale (VAS) for pain, and the original survival prediction tool (SPT) or that envisioned by Nieder. 19,22,27,[30][31][32]35 In addition to these scales, there are others that can be used in the evaluation of patients with spinal metastases, adding more detailed aspects and with a multidisciplinary view of the patient centered on functional capacity, functional independence/physical performance, on the presence of comorbidities, the quality of life and satisfaction, on the presence of depression and mood disorders, on functional activity to return to work, but, due to Brazilian sociocultural peculiarities, the results may not be fully applicable in their entirety. 19,25,[54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] Another aspect to be mentioned is that a decision centered only on prognostic scales can often produce inhuman situations for the patients and their families, characterizing for them a feeling of abandonment and discredit. In one study, patients who scored between 0 and 8 on the modified Tokuhashi scale and who normally would not have been operated on because of poor prognosis, underwent surgery and had a longer survival than expected from the score, showing the benefit of investing in patients with worse prognoses. 64 In this context, despite the numerous scales available to assist with therapeutic indications and their validity in determining the prognosis in treatment of spinal metastasis, a multidisciplinary team is essential to evaluate individual patient factors that go beyond the physical area, such as functional performance, neurological deficit, spinal instability, psychological and emotional state, involving their uniqueness, their values, and their beliefs. 66,67,[69][70][71] The thematic unit "types of treatment" in spinal metastases includes the minimally invasive and traditional categories, the former being predominantly cited.
The treatment is associated with the diagnosis of the spinal metastases with the investigation of the symptoms present in 10% of patients: • Pain: In 83-95% of the patients, pain precedes the development of other neurological symptoms by weeks or months. Localized pain is the result of intrabone pressure and, with the evolution of bone changes, pain is precipitated by movement (mechanical pain) or involves the nerve endings through compression of the spinal cord causing the often acute pain that follows the path of the compromised nerve To evaluate the intra-and interobserver concordance of the SINS, Harrington, Tokuhashi, and Tomita scores.

Retrospective reproducibility study
Predictive instability scores -Harrington, prognostic -Tomita, have higher intra-and interobserver reliability among spinal surgeons with more than 10 years of experience. The SINS score -election for daily practice and the most frequent capable of modifying the conduct. To evaluate the performance of the Tokuhashi score in a cohort of 260 patients and to look for other variables that can improve the forecasting of results prior to surgery.

Retrospective single center cohort
It supports the validity and reproducibility of Tokuhashi. Our discovery that less time for the diagnosis of metastases and age ≥ 70 year also were significantly associated with survival in our populations; suggests additional effort to improve and update the Tokuhashi score.

2B B
Prognostic factors in patients with symptomatic spinal metastases and normal neurological function 32 To evaluate potential prognostic factors to predict survival after radiotherapy in patients with painful spinal metastases and normal neurological function.

2B B
Results and toxicity for imageguided hypofractionated stereotactic radiosurgery for metastatic spinal sarcomas 35 To investigate whether hypofractionated (HF) or single fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) can effectively control the lesions.

Retrospective cohort
In most of series of metastatic spinal sarcomas of the study imageguided single fraction stereotactic radiosurgery demonstrated minimal toxicity and excellent local control.

2B B
root (radicular pain), in addition to the possibility of referred pain in a location distant from the metastases in cases of lumbar spinal cord compression. For localized pain, non-steroidal or steroidal anti--inflammatories are used. For radicular pain, interlaminar or transforaminal epidural steroid injections are usually applied. In mechanical pain, it recommended to stabilize the spine as conventional or minimally invasive arthrodesis, vertebroplasty, kyphoplasty, stereotactic radiosurgery or surgery traditional as vertebrectom. 7,29,[72][73][74][75][76][77][78][79][80][81][82][83][84] • Fracture: Sometimes fractures are the first symptom associated with pain. The thoracolumbar region is the most frequent site of spinal fractures. The treatment can be radiotherapy, conventional or minimally invasive arthrodesis, vertebroplasty, kyphoplasty, stereotactic radiosurgery or traditional surgery. [85][86][87][88][89][90] • Spinal cord compression: 5 to 10% of patients have spinal cord compression. Usually there is a report of lumbar or cervical pain, paresthesia, loss of physical strength in the area of the body below the tumor, difficulties with mobility of the upper or lower limbs depending on its location leading to paraplegia or quadriplegia, and difficulties with urinary (incontinence or retention) and intestinal (fecal incontinence) function. It demands immediate attention through the administration of corticosteroids, radiopharmaceuticals, or radiotherapy. Decompression surgery is indicated when the affected area was previously submitted to unsuccessful radiotherapy or when there was neurological deterioration during the radiotherapy procedure, and when the spine is unstable and there are not multiple zones of compression, vertebroplasty, kyphoplasty, or stereotactic radiosurgery can be performed. 72,[78][79][80][81] • Hypercalcemia is present in 20 to 44% of patients (release of calcium from bone destruction), characterized by the progressive decline of cognitive ability, stupor, and coma, as well as polyuria, anorexia, nausea, and vomiting, which undiagnosed can lead to death. Treatment is essential to providing the patient the possibility of undergoing treatment directed at the neoplasia. Calcium should be avoided whether in parenteral nutrition or present in medications, sedatives should be reduced to improve the level of consciousness, and hydration and expansion of circulating volume should be achieved. Other treatments include phosphate repositioning, administration of glucocorticoids to reduce intestinal absorption, and antiresorptive medications, such as bisphosphonates like zoledronic acid. 73,[82][83][84][85] The diagnosis should also be conducted using imaging exams, such as X-rays, magnetic fields, or radioactive substances. The X-ray can show signs of dissemination of the disease to the bones in osteolytic or lytic metastases, due to destruction of the bone. Osteoblastic or blastic metastases appear as darker gray-white areas in the bone image, because due to the non--reabsorption of bone the area of bone appears denser. X-rays can also show fractures in bones weakened by metastases. Bone scintigraphy shows the presence (or not) of bone metastases, as areas of bone damage appear as dark spots in the image of the skeleton. In addition to these, there are computed tomography and/or magnetic resonance with and without contrast, positron emission tomography or PET scan, which enables detection of whether the cancer has spread to the lymph nodes or to other body structures and organs, and also needle or incisional biopsy, and laboratory tests of tumor markers, calcium and alkaline phosphatase, and N-telopeptide (urine). [82][83][84][85][86] The predominance of articles in the literature on minimally invasive surgical procedures in the treatment of spinal metastases agrees Evaluation of the interobserver reproducibility of a new scale for orientation of therapeutic conduct in spinal metastases: SINS score (Spine Instability Neoplastic Score) 25 Effectiveness of surgical intervention in the quality of life and survival of patients with metastatic lesions of the spine 22 Tokuhashi Score and other prognostic factors in 260 patients with surgery for spinal metastases 31 Prognostic factors associated with the survival of patients with symptomatic bone metastases: retrospective cohort study of 1,043 patients 27 Prognostic factors in patients with symptomatic spinal metastases and normal neurological function 32 Score evaluation in decision-making in spinal metastases 30 26 Spinal metastasis in thyroid cancer 28 Patients with spinal metastases submitted to neurology decompression and stabilization 29 Prognostic factors in patients with symptomatic spinal metastases and normal neurological function 32 Results and toxicity for image-guided hypofractionated stereotactic radiosurgery for metastatic spinal sarcomas 35 Traditional Regensburg Protocol for Spinal Mestastases 23 Management of metastatic spinal neoplasias -an update 24 Prognostic Scale Effectiveness

Higher Probability
Overall survival following reirradiation of spinal metastases -independent validation of predictive models 19 Single center prospective study of the efficacy of percutaneous cement reinforcement in the treatment of fractures with vertebral compression 21 Tokuhashi Score and other prognostic factors in 260 patients with surgery for spinal metastases 31 Prognostic factors in patients with symptomatic spinal metastases and normal neurological function 32 The Oswestry Risk Index: an aid in the treatment of metastatic spinal disease 34 Lower Probability The Tokuhashi Scale has limited applicability to most patients with medullary compression secondary to spinal metastasis 18 with the current trends that also consider this treatment the most appropriate for local control of the disease, improved performance and neurological function, and pain control, with minimal possibility of morbidity. 4,69,75,79,87,90,91 The most commonly used minimally invasive techniques are vertebroplasty, kyphoplasty, and stereotactic radiosurgery. Vertebroplasty consists of a percutaneous injection of fast-fixing bone cement inside the vertebral body, whereas kyphoplasty involves the prior dilatation of the collapsed vertebral body to form a cavity that allows the introduction of the cement with gradual pressure. These procedures are performed under the guidance of radioscopy or computed tomography. These techniques successfully stabilize the vertebral body with pain relief in 75% to 85% of patients. 24,73,74,92,93 Stereotactic radiosurgery (SRS) of the bone is an emerging technique that involves the administration of high doses of radiation to a given region, in a single treatment fraction or in a few fractions, and is a safe and effective treatment modality for small, well-defined tumors, in addition to having advantages for the patient of low toxicity risk, and reduction of the number of visits for treatment and the associated costs. It involves a specific multidisciplinary decision for each patient, especially with radio-resistant tumors like sarcoma, melanoma, renal cell carcinoma, non-small-cell lung cancer, and carcinoma of the colon. [93][94][95][96][97] Another aspect to be considered in the treatment of spinal metastases is the protocol of the North American hospital, the Memorial Sloan-Kettering Cancer Center, used to determine the ideal therapy for patients based on four fundamental evaluations: Neurological, Oncological, Mechanical Stability, and Systemic Disease (NOMS), not cited in the articles selected for this study. 98 In the neurological aspect of NOMS, the presence of neurological deficit with signs of myelopathy and radiculopathy and the degree of spinal cord compression are evaluated. In the oncological area, the characteristics of the tumor and its susceptibility to radiotherapy are studied. In mechanical instability, the SINS is used, and the presence of fractures is verified in order to consider the need for vertebroplasty, kyphoplasty, or traditional surgery. The systemic aspect seeks to identify the extent of the disease and comorbidities, verifying tolerance to treatment. Thus, the expected overall survival of the patient is based on the extent of the disease and the histology of the tumor. 98,99 The objective of NOMS is to provide a dynamic infrastructure for the treatment of spinal metastases with the ability to incorporate advances in interventionist radiology, radiation, medical oncology, and surgical techniques to optimize patient outcomes. In addition, NOMS provides a single language for all the professionals, since as these treatment decisions become more complex, an evidence-based, multidisciplinary approach, including oncologists, physicians, radiation oncologists, surgeons, interventionists, and pain specialists is necessary. 97,98 Regarding the thematic unit "prognostic scale effectiveness", in the articles found there is a predominantly greater probability that these scales indicate the survival of patients with bone metastases more accurately, even though they are many times exhaustive because they involve various measures and time availability, which led one of the articles to advise against the use of scales. [97][98][99] However, the use of scales is useful and essential as it often helps professionals to broaden their ability to predict cancer patient survival, although this expectancy is relative and may be lengthened or shortened, regardless of the clinical experience of the professional or the overall knowledge about the patient. 100 CONCLUSION By conducting this study, it was possible to identify, enumerate, and analyze articles that address the treatment and prognosis of spinal metastases. The fact that there were 19 articles shows that there is research and scientific production in this area. The thematic units and their categories, treatment decision -prognostic scales or clinical neurological evaluation, types of treatment -minimally invasive or traditional, and prognostic scale effectiveness, provide insight into the different possibilities for patient assessment and their applicability in practice.
When making the diagnosis, planning the treatment, and establishing a prognosis, the professional should be aware and deliberate actions based on the objective and the essentially subjective characteristics of the patients, such as beliefs and values, which though immeasurable, influence survival and the efficacy of the treatment.
This study leads to reflection about the treatment of spinal metastases, shedding light on scientific production. The decision about treatment should be based individually on the understanding of each surgeon and of the clinical situation of each patient and the greater the knowledge acquired, the lower the risk and the greater the benefits for the patient, affecting the positive prognosis.
It is up to the professional to care for these patients with optimism and determination, understanding that cancer and its metastases may involve finitude, but it is common for all human beings and should be experienced with dignity, comfort, and respect.