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Management of symptomatic spine metastases: A multidisciplinary approach based flow-chart
Manejo de metástasis sintomáticas de columna: un enfoque multidisciplinario basado en un diagrama de flujo
V. Pipolaa,
Corresponding author
valeriopipola@gmail.com

Corresponding author.
, S. Pasinia, R. Ghermandia, M. Girolamia, L. Falzettia, S. Pérezb, T. Basb, A. Gasbarrinia
a Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
b Spine Unit, Department of Orthopedic Surgery and Traumatology, La Fe University and Polytechnic Hospital of Valencia, Avinguda de Fernando Abril Martorell, 106, 46026 Valencia, Spain
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To date&#44; there is still no universally accepted treatment line&#44; due to the great variety of histotypes of primary tumors and their method of metastasis&#46; However&#44; what is universally accepted is that bone metastasis is just an element of a systemic disease&#44; therefore patients management require a multidisciplinary approach&#44; involving oncologist and a radiotherapist&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most frequent clinical presentation of a patient affected by vertebral localizations of disease is pain&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> It is usually a pain that is poorly responsive to most analgesic drugs&#44; and it is often underestimated and attributed to problems of a degenerative nature&#44; delaying the diagnosis and the correct diagnostic and therapeutic classification of the patient&#46; The pathological mechanism that determines pain is usually due to one of the following mechanisms&#44; or a combination of several of them&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><p id="par0040" class="elsevierStylePara elsevierViewall">cortical bone expansion with periosteal stretching and nociceptor activation&#59;</p></li><li class="elsevierStyleListItem" id="lsti0010"><p id="par0045" class="elsevierStylePara elsevierViewall">direct compression exerted by the tumor on the spinal cord or nerve roots&#46;</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">The progressive replacement of healthy tissue by pathological tissue&#44; which not having the same biomechanical properties of healthy bone&#44; can lead to vertebral instability&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The presence of pathological fractures&#44; which typically manifest with acute onset pain&#44; in the absence of apparent trauma&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Another modality of presentation of vertebral metastases&#44; but less frequent than pain&#44; are symptoms of a neurological nature&#46; These can arise from direct compression on the spinal cord or nerve roots&#44; or compression given by bone fragments or bone deformities arising following a pathological fracture&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The first step in the correct management of the patient with vertebral metastases is to make the correct diagnosis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Vertebral metastases can have three different presentation patterns&#58; osteolytic &#40;lytic&#44; destructive&#41;&#44; osteoblastic &#40;blastic&#44; productive&#41;&#44; or mixed&#46; Lytic lesions appear destructive&#44; showing loss of both cancellous bone and cortex&#44; and are usually well circumscribed&#46; Blastic lesions&#44; on the other hand&#44; appear hyperdense and are typically expansive and with poorly defined borders&#46; Mixed lesions have both lytic and blastic features&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Lytic lesions can weaken the structure of the vertebra&#44; resulting in impending fracture&#44; while blast lesions can create neurological problems by exerting compressions on the spinal cord and roots&#46; CT scan allows these lesions to be evaluated and classified as lytic&#44; blast or mixed&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The importance of better assessing the bone quality in metastatic lesions is demonstrated in several studies&#44; which show only a 2&#46;3&#37; risk of pathological fracture when &#60;50&#37; cortical bone is involved&#44; but an 80&#37; risk of pathological fracture when &#62;75&#37; of cortical bone is involved&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">However&#44; the imaging in the diagnosis process is enough for a few pathognomonic lesions &#40;e&#46;g&#46;&#44; Osteoid osteoma&#41;&#44; the laboratory is helpful for a few others &#40;e&#46;g&#46;&#44; multiple myeloma&#41;&#44; but histological diagnosis is required for the majority&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">It is therefore necessary to obtain a tissue specimen&#44; and in the spine&#44; the technique of choice is through a transpedicular CT-guided biopsy&#46; This is the best option because it is the one with the lowest risk of local dissemination of disease and allows&#44; if indicated&#44; surgical excision of the biopsy tract&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Modern treatments of medical therapy &#40;chemo-&#44; hormonal-&#44; immuno-&#41; and radiotherapy have certainly increased the survival of most patients suffering from solid and hematologic tumors&#44; however they are not often able to effectively control pain and functional impairment&#46; Novel tumor biomarkers and tumor epigenetics along with novel hormonal and immunotherapeutic will perhaps positively skew the survival curves even more given better disease control&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The aim of surgery in the management of spine metastases might be one&#44; or an association&#44; of the following&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">Neurological function preservation or recovery from a neurological deficit&#59;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">Pain relief&#59;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Spinal stability restoration&#59;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Local control of the tumor&#46;</p></li></ul></p><p id="par0125" class="elsevierStylePara elsevierViewall">Even though local control of the tumor is a target of the treatment of metastases&#44; it is not always achieved surgically&#46; In fact&#44; the wide variety of histotypes which may deposit in the spine differs in the sensitivity to non-surgical treatments &#40;such as RT&#44; hormonal therapy&#44; and immunotherapy&#41;&#46; Moreover&#44; it is intuitive that the longer the expected survival of the patient is&#44; the greater is the possibility that the disease might relapse &#40;with eventual compression of the spinal cord and&#47;or pathological fracture&#41;&#44; thus the differential importance of achieving durable local control&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">It is important for the surgeon to be aware of the various options available to achieve local control of the various different histotypes&#44; whether surgical or not&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">From our prospective the surgical techniques in spine metastasis can be summarized into &#40;1&#41; decompression and stabilization&#44; &#40;2&#41; intralesional excision &#40;curettage or debulking&#41;&#44; and &#40;3&#41; en-bloc resection&#44; these latter two followed by reconstructive procedures &#40;with various techniques&#41;&#46; All these operations can be performed by either the anterior&#44; posterior&#44; or combined approaches&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">1&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Decompression and stabilization&#58; This is the quickest and least aggressive surgical procedure&#46; It can be performed anteriorly or posteriorly through open or minimally invasive approaches or posteriorly&#46; Combined approaches are not commonly used in this setting&#46; A decompressive laminectomy with or without removal of the epidural tumor is combined with posterior stabilization&#46; The authors believe that it is mandatory to stabilize the spinal column at the same time&#46; This procedure is indicated for patients with short-term prognosis who may have neurologic compromise and&#47;or a pathological fracture&#46; Surgeon familiarity and efficiency with these techniques allows this procedure to be performed in an urgent or emergent setting&#46; Anterior decompression and stabilization is more commonly associated with visceral and vascular complications&#59; thus&#44; fewer centers recommend this approach&#46; Preoperative selective arterial embolization can decrease blood loss associated with vascular tumors like renal cell carcinoma and thyroid carcinoma&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">2&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Intralesional excision &#40;curettage or debulking&#41;&#58; The tumor is directly approached either anteriorly&#44; posteriorly&#44; or circumferentially and removed in a piecemeal fashion in order to achieve circumferential decompression of the spinal cord and decrease tumor burden&#46; This procedure is often performed as part of a multidisciplinary approach and is preceded by selective preoperative arterial embolization for select tumors&#46; This operation is indicated for metastases not sensitive to radiotherapy associated with a pathological fracture or spinal cord compression or when a tumor debulking is recommended to enhance oncological treatments&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">3&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">En-bloc resection&#58; This procedure is most commonly performed for patients with primary malignant bone tumors&#44; and it is occasionally recommended for a patient who has a middle- to long-term prognosis and a solitary metastasis from a tumor that is relatively resistant to chemotherapy and radiotherapy&#46; The operation can be performed by a posterior approach alone or a combined anterior and posterior approach&#46; En-bloc resection is associated with a lower local recurrence rate&#44; but the risk-to-benefit ratio is very high due to the morbidity of these long operations &#40;8&#8211;16<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; En-bloc resection is also considered in highly vascularized tumors as this type of resection may lead to less blood loss than an intralesional excision&#46; In most of the cases&#44; a spine metastasis with such a relevant encroachment of the canal to provoke a cord symptomatic compression is not suitable to en-bloc resection due to the lack of the surgical criteria to perform such kind of procedure&#46; Adjuvant treatment &#40;i&#46;e&#46;&#44; RT&#44; hormonal therapy&#41; may decrease the incidence of local recurrence and distant progression of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a></p></li></ul></p><p id="par0155" class="elsevierStylePara elsevierViewall">In choosing the most appropriate treatment&#44; several elements must be taken into consideration&#58; patient&#39;s prognosis&#44; the general conditions of the patient&#44; the histotype of the tumor and its sensitivity to adjuvant treatments&#44; the spread of the disease and the neurological conditions&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In the past&#44; many efforts have been made in the attempt to create prognostic scores that could guide the surgical management&#46; With these systems&#44; each parameter is assigned a score and the sum of these scores indicates the most appropriate treatment&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Tokuhashi et al&#46; reported their &#8220;Scoring system for preoperative evaluation of a patient&#39;s prognosis with metastatic spinal tumor&#8221; in 1989&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> It was based on retrospective data collected from 64 patients with spinal metastases and analyzed to develop a comprehensive scoring system identifying six variables on which assess prognostic stratification&#46; A revised version published in 2005 were the item of &#8220;Primary site of cancer&#8221; were modified&#46; According to this score&#44; three classes of tumor management are calculated&#58; conservative management &#40;score 0&#8211;8&#41;&#44; palliative surgery &#40;score 9&#8211;11&#41; and excisional surgery &#40;score &#62;12&#41; with predicted survival reported at &#60;6&#44; &#62;6 and &#62;12 month respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Tomita et al&#46; proposed in 2001 a prognostic score base on three factors&#58; the rate of growth of primary tumor&#44; the number of bone metastases and presence&#47;absence pf visceral metastases&#46; The score of the three components are added together to produce an overall score ranging from 2 to 10 from good to poor prognosis respectively&#46; They did not evaluated the performance status because it was considered a reflection of tumor load&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Many other score have been developed along the years but none of them showed more than 90&#37; consistency between the predicted and the actual survival time to be used in the clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Factors influencing the incidence of complications and survival after surgical treatment of spinal metastases were analyzed and it was observed that preoperative neurological conditions&#44; the nature of the primary tumor and the extent of spinal involvement&#44; are the main determining factors&#46; The systemic spread of the disease or the age of the patient affect the outcome less&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Therefore&#44; both the type of patient and the type of surgical treatment proposed must be carefully selected&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In 2004 the main author &#40;AG&#41; proposed an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Each patient follows his own &#8220;personal&#8221; sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual&#46; For instance&#44; a patient in general poor condition with a high &#8220;ASA&#8221; score is usually not a candidate for surgery&#44; regardless of the primary tumor nature or the number of metastases&#46; For this patient&#44; the most important element would be the sensitivity of the tumor to adjuvant treatment&#46; Similarly&#44; a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Therefore&#44; patient is not considered only in terms of disease&#44; reducing the choice of treatment to an oversimplified mathematical score&#44; but the patient is studied as a whole&#58; first considering his general conditions&#44; and only subsequently the elements related to the metastatic disease&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The proposed treatment algorithm starts from the diagnosis of spinal metastases&#46; Subsequently the first step is the anesthesiological evaluation&#44; during which the operability of the patient must be established&#58; if the patient were inoperable &#40;high ASA&#41;&#44; non-surgical options would be considered&#46; The next step takes into consideration the histotype and its sensitivity to adjuvant therapies&#58; if the tumor does not respond to any form of treatment&#44; the only option for the patient would become pain therapy&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">If the patient is judged operable&#44; the extent of spinal cord compression and the severity of the neurological damage are assessed&#46; If a neurological deficit is present&#44; the possibility of recovery is evaluated based on the time since the onset of symptoms &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">If a neurological recovery is excluded at this stage&#44; the sensitivity to adjuvant treatments should be re-evaluated&#46; On the other hand&#44; if the patient has an acute and progressive spinal cord injury&#44; emergency surgery must be performed&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">If there is no neurologic deficit or the damage is stable&#44; sensitivity to adjuvant treatments is evaluated&#46; If the tumor is not responsive and an isolated metastasis is present&#44; resection of the lesion may be chosen &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Surgical decompression and stabilization are indicated instead if the metastases are multiple and are treatable&#46; If they are not treatable&#44; only pain therapy will be administered&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0225" class="elsevierStylePara elsevierViewall">When there is no deficit or the lesion is recoverable&#44; and the tumor is responsive to some form of adjuvant treatment&#44; the pathologic fracture &#40;actual or impending&#41; is evaluated&#46; In fact&#44; this parameter is crucial in guiding the choice toward surgical decompression and stabilization treatment&#44; or adjuvant treatment alone&#46; Tumor resection can be performed en-bloc with a wide margin or by intralesional debulking&#46; In general&#44; en-bloc excision is suggested by the authors in case of isolated metastases of histotypes unresponsive to radio- and chemo-therapy treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Level of evidence</span><p id="par0230" class="elsevierStylePara elsevierViewall">Level of evidence <span class="elsevierStyleSmallCaps">iv</span>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflict of interests</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors declare they have no conflict of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We described an algorithm for the management of spinal metastases in which the importance of single parameters varies depending on when they are contemplated&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Each patient follows his own &#8220;personal&#8221; sequential process which does not necessarily consider all the parameters each time as some may be irrelevant for the purpose of choosing the type of treatment for that single individual&#46; For instance&#44; a patient in general poor condition with a high &#8220;ASA&#8221; score is usually not a candidate for surgery&#44; regardless of the primary tumor nature or the number of metastases&#46; For this patient&#44; the most important element would be the sensitivity of the tumor to adjuvant treatment&#46; Similarly&#44; a patient with acute and progressive spinal cord injury would undergo surgical decompression and stabilization without considering a more strenuous intervention&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Describimos un algoritmo para el manejo de las met&#225;stasis espinales en el que la importancia de los par&#225;metros individuales var&#237;a dependiendo del momento en el que se contemplan&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Cada paciente sigue su propio proceso secuencial &#171;personal&#187; que no necesariamente considera todos los par&#225;metros cada vez&#44; ya que algunos pueden ser irrelevantes para el prop&#243;sito de elegir el tipo de tratamiento para ese individuo&#46; Por ejemplo&#44; un paciente en mal estado general con una puntuaci&#243;n alta de &#171;ASA&#187; generalmente no es candidato para la cirug&#237;a&#44; independientemente de la naturaleza del tumor primario o el n&#250;mero de met&#225;stasis&#46; Para este paciente&#44; el elemento m&#225;s importante ser&#237;a la sensibilidad del tumor al tratamiento adyuvante&#46; Del mismo modo&#44; un paciente con lesi&#243;n aguda y progresiva de la m&#233;dula espinal se someter&#237;a a descompresi&#243;n quir&#250;rgica y estabilizaci&#243;n sin considerar una intervenci&#243;n m&#225;s agresiva&#46;</p></span>"
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                      "titulo" => "WHO report on cancer&#58; setting priorities&#44; investing wisely and providing care for all"
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                    0 => array:2 [
                      "titulo" => "Complication&#44; survival rates and risk factors of surgery for metastatic disease of the spine"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;J&#46; Wise"
                            1 => "J&#46;S&#46; Fischgrund"
                            2 => "H&#46;N&#46; Herkowitz"
                            3 => "D&#46; Montgomery"
                            4 => "L&#46;T&#46; Kurtz"
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                      "doi" => "10.1097/00007632-199909150-00014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Spine"
                        "fecha" => "1999"
                        "volumen" => "24"
                        "paginaInicial" => "1943"
                        "paginaFinal" => "1951"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10515021"
                            "web" => "Medline"
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                      "titulo" => "Role of vertebral veins in metastatic processes"
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                          "autores" => array:1 [
                            0 => "O&#46;V&#46; Batson"
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                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Intern Med"
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