Clinical management of spinal metastases—The Dutch national guideline

European Journal of Cancer 104 (2018) 81e90

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Clinical management of spinal metastasesdThe Dutch national guideline Laurens Bollen a, Sander P.D. Dijkstra b, Ronald H.M.A. Bartels c, Alexander de Graeff d, Davey L.H. Poelma e, Thea Brouwer f, Paul R. Algra g, Jos M.A. Kuijlen h, Monique C. Minnema i, Claudia Nijboer j, Christa Rolf k,1, Tebbe Sluis l, Michel A.M.B. Terheggen m, Alexandra C.M. van der Togt-van Leeuwen n, Yvette M. van der Linden o, Walter Taal p,* a

Amsterdam UMC, University of Amsterdam, Department of Radiotherapy, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands b Leiden University Medical Center, Department of Orthopedics, P.O. Box 9600, 2300 RC Leiden, the Netherlands c Radboud University Medical Center, Department of Neurosurgery, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands d University Medical Centre Utrecht, Department of Medical Oncology, P.O. Box 85500, 3508 GA Utrecht, the Netherlands e Radiotherapy Institute Friesland, Borniastraat 36, 8934 AD Leeuwarden, the Netherlands f National Federation of Cancer Patient Organizations, P.O. Box 8152, 3503 RD Utrecht, the Netherlands g Alkmaar Medical Centre, Department of Radiology, P.O. Box 501, 1800 AM Alkmaar, the Netherlands h University Medical Centre Groningen, Department of Neurosurgery, P.O. Box 30001, 9700 RB Groningen, the Netherlands i UMC Utrecht Cancer Center, Department of Hematology, P.O. Box 85500, 3508 GA Utrecht, the Netherlands j VU University Medical Center, Department of Neurology, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands k Community Health Center Hardijzer en Rolf, Jel Rinckesstrjitte 2, 8851 ED Tzummarum, the Netherlands l Rijndam Rehabilitation Centre, SCI Unit, Westersingel 300, 3015 LJ Rotterdam, the Netherlands m Rijnstate, Department of Anesthesiology, Pain Medicine and Palliatieve Care, P.O. Box 9555, 6800 TA Arnhem, the Netherlands n Netherlands Comprehensive Cancer Organization (IKNL), Vasteland 78, 3011 BN Rotterdam, the Netherlands o Leiden University Medical Center, Department of Radiotherapy, Centre of Expertise Palliative Care, P.O. Box 9600, 2300 RC Leiden, the Netherlands p Erasmus MC Cancer Institute, Department of Neuro-Oncology/Neurology, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands Received 4 June 2018; received in revised form 22 August 2018; accepted 29 August 2018

* Corresponding author. E-mail address: [email protected] (W. Taal). 1 Currently retired. https://doi.org/10.1016/j.ejca.2018.08.028 0959-8049/ª 2018 Elsevier Ltd. All rights reserved.

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KEYWORDS Spinal metastasis; Guideline; Metastatic epidural spinal cord compression; Diagnostics; Treatment

Abstract This article is a summary of the revised Dutch multidisciplinary evidence-based guideline ‘Spinal metastases’ (English translation available at: https://www.oncoline.nl/ spinal-metastases) that was published at the end of 2015. This summary provides an easyto-use overview for physicians to use in their daily practice. ª 2018 Elsevier Ltd. All rights reserved.

1. Introduction The revised Dutch multidisciplinary evidence-based guideline ‘Spinal Metastases’ was published at the end of 2015 (English translation available at: https://www. oncoline.nl/spinal-metastases). The previous Dutch guideline ‘Spinal Epidural Metastases’ dated from 2006, and at the start of the current revision, it was decided to extend the guideline to a multidisciplinary, evidence-based guideline ’Spinal Metastases’. To ensure a broad basis for the guideline, a multidisciplinary working group was installed, representing all medical specialists involved in the treatment of spinal metastases, as well as a nurse practitioner, a general practitioner and a patient representative. Spinal localisations of multiple myeloma and lymphoma were included in the revised guideline because the symptoms, the complications and the treatment of spinal localisations of haematological malignancies show many similarities with those of spinal metastases from solid tumours. Before the revision, the most important bottlenecks were identified through an extensive survey among professionals and patients. The guideline committee selected three problem areas to be answered evidence based and in addition, a large number of bottlenecks were answered consensus based. The literature search for evidence-based questions was conducted and supervised by methodological experts from the Netherlands Comprehensive Cancer Organization. The resulting guideline provides recommendations in the field of diagnostics, patient selection for the various treatment modalities, organisation of care, the follow-up program and palliative care. Patient information was also included as it was not yet available. Publications about this guideline include two articles in Dutch [1,2] and an English [3] publication which focusses on the process and the methodology of the realisation of the guideline. This article is a summary of the guideline and provides an easy-to-use overview for physicians to use in their daily practice. 2. Background Owing to an increase in overall cancer survival and the ageing population, the incidence of spinal metastatic

disease is increasing [4e7]. Several types of spinal metastases are recognised. Intramedullary metastases are located within the spinal cord itself, whereas leptomeningeal metastases are located within the subarachnoid space. These types of spinal metastases are quite rare and are usually seen in the end-stage disease. Spinal epidural metastases are located on the outside of the dura mater, and the vast majority originates from the osseous parts of the spinal column. These spinal bone metastases (SBMs) are the most frequently observed osseous metastases and are surpassed in number only by lung and liver metastases [8]. More than two-thirds of all SBMs are caused by breast, lung and prostate cancer. Less frequently observed primary malignancies are colon, kidney and upper gastrointestinal cancers [9,10]. The current guideline concerns only SBMs with and without epidural expansion. 3. Clinical presentation Depending on their size and location, SBMs can cause pain and/or neurologic deficits. In 90e95% of patients with SBMs, pain is the first presenting symptom [11,12]. Patients can experience pain because of either fracturing or collapsing of the vertebral body, pressure on the periosteum from within the vertebra, or nerve root and spinal cord compression. Physical examination in the case of suspected SBMs is not very specific but can provide indispensable clues on the location of disease within the spinal column and the extent of nerve root and spinal cord compression. Radiating pain and numbness are indicative of nerve root compression, which should follow certain dermatomes. Symptoms of nerve root compression generally increase with increased intra-abdominal pressure, such as when coughing. Spinal deformity such as kyphosis can be noticed in patients after collapse of the vertebral body. Pain decreasing with recumbency can point to spinal instability; however, patients with metastatic kyphosis could experience an increase in pain while recumbent. Also patients with mechanically stable SBMs can have nightly pain, probably because of the pressure of the SBM. Neurological deficits are indicative of spinal cord compression. Table 1 summarises the most common presenting symptoms of progressive SBMs.

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Table 1 Alert symptoms and causes of progressive SBMs, before developing paraplegia or cauda equina syndrome. Symptom

Cause

(Nightly) pain in the back Sudden and severe back pain Deformity (kyphosis/scoliosis) Localised back pain decreasing with recumbency Radiating pain/numbness Weakness of limbs Ataxia/gait abnormality Symmetric paraesthesia radiating down the body

Spinal metastasis Vertebral body fracture Vertebral body fracture Spinal instability Nerve root compression Spinal cord compression Spinal cord compression Spinal cord compression

Awareness of SBMs is essential as they can compromise the spinal cord or cauda equina, leading to paraplegia, tetraplegia or cauda syndrome. This malignant epidural spinal cord compression (MESCC) occurs approximately in 1e5% of all patients with SBMs [13e15] and is an indication for emergency treatment. In patients with a malignancy presenting with back pain, the chance of finding MESCC on magnetic resonance imaging (MRI) is 3e10%, increasing up to 65e70% if they present with clinical signs of myelopathy or compression of the cauda equina [13,16]. Finally, assessing the extent and duration of neurologic deficit is essential as it determines the urgency with which additional imaging should be performed. 4. Imaging For the detection of spinal metastases, MRI of the whole spine is superior to all other imaging modalities. It is capable of showing osseous metastatic disease and providing essential information on spinal cord and nerve root compression [17e19]. It is recommended that the MRI consists of sagittal T1- and T2-weighted images of the entire spine and axial T2-weighted images through the affected spinal levels [20,21]. SBMs are generally hypointense on T1-weighted images, and depending on their lytic or blastic characteristics, can be hyperintense or hypointense on T2-weighted images, respectively. Contrast enhancement is not required for demonstrating SBMs, and contrast-enhanced T1-weighted images may even obscure SBMs. Therefore, the MRI for detection of SBMs should always include T1-weighted images before contrast administration. However, leptomeningeal metastatic disease can be missed without the addition of contrast. The urgency of acquiring imaging should depend on clinical symptoms. As functional recovery after neurologic deficit is dependent on the duration of symptoms and preservation of the ambulatory status, we recommend obtaining an MRI immediately in case of possible MESCC or bilateral radicular symptoms [22,23]. If there is unilateral motor and/or sensory deficit indicative of radicular compression, an MRI should be obtained within 24e48 h, depending on the speed of progression.

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In case of unilateral radicular pain, an MRI should be obtained within 1 week, and in case of localised pain, within 2 weeks. If an MRI is not available, a spiral computed tomography (CT) with reconstruction after intravenous or intrathecal contrast can be considered, but for diagnosing SBMs, conventional X-rays, bone scintigraphy and positron-emission tomography(PET)eCT are generally not recommended. All modalities provide no reliable information on the extent of soft tissue involvement and require increasing levels of bone marrow invasion and cortical destruction, before the lesion will become apparent (Fig. 1). In addition, bone scintigraphy will yield false-negative results in the case of purely lytic metastases, and sensitivity and specificity of a PETeCT are dependent on which tracer is used and the specific uptake characteristics of the tumour involved. 5. Unknown primary and further work-up In patients with SBMs of unknown origin, it is advised to make an urgent PETeCT of the thorax/abdomen and (if possible) to postpone corticosteroids until after the biopsy as this can interfere with making the histological diagnosis in case of haematological malignancies. Tissue for histology (and possibly microbiology) should be obtained before starting the treatment. In the case of clinical or radiological MESCC, the tissue should be obtained within 1 day or within 72 h, respectively. Optionally, the treatment can be started immediately after the biopsy, pending the histological diagnosis. Histology can be obtained from the epidural mass itself or from another mass that is more easily accessible. In

Fig. 1. Imaging modalities in spinal metastases. The figure shows which pathological stages (horizontal axis) become visible with the various modalities (vertical axis). The presence of bone marrow metastases first becomes visible with an MRI. If the SBMs induce increased osteoblastic activity, the Tc-MDP scan is positive. The initial stage of bone destruction in case of increased osteoclastic activity is made visible by a CT. Advanced destruction is visible on conventional X-rays. MRI, magnetic resonance imaging; CT, computed tomography; SBMs, spinal bone metastases; Tc-MDP, technetium medronic acid.

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case of an instable spine, immediate stabilising surgery can be considered. In addition to SBMs, back pain, radiculopathy and signs of MESCC in a patient with cancer can also be caused by a degenerative, infectious, inflammatory, or traumatic process (see Table 2). The diagnostic process described previously is summarised in the flowchart depicted in Fig. 2.

participate in case of a possible operation indication (see Fig. 3). It is recommended to start the treatment within 24 h in case of clinical MESCC, within 72 h with only radiological MESCC and within 14 days in case of only pain.

6. Treatment of SBMs

7.1. Survival prediction

Treatment selection for symptomatic SBMs should at least depend on expected survival, the condition of the patient, the number and localisation of involved vertebrae and the degree of expansion of the SBM in the surrounding tissue. Determining the best treatment for a patient with SBMs requires a multidisciplinary approach. In general, discussing a patient in an oncological multidisciplinary consultation (MC) has added value with respect to selection of the best and most suitable treatment options. The MC may also lead to a proactive policy regarding spinal metastasis, with attention to any long-term risks when the disease progresses. This proactive policy could consist of handing out a patient information form with the symptoms that require patients to (urgently) contact their treating physician (see Appendix 1 of the guideline) and make the treating physician aware of starting local and/or systemic therapy in an early stage in case of an asymptomatic SBM showing a potential risk of mechanical instability and/or MESCC. A study by Fitzpatrick demonstrates that the number of incorrect referrals of patients for SBM surgery reduced if prior virtual consultation (by email, telephone and imaging via the online picture archiving and communication system (PACS) system) with the neurosurgeon takes place [24]. All specialists involved in the treatment of SBMs should participate in this MC: the originally treating specialist, a radiation oncologist, a medical oncologist and a radiologist. A neurologist should be present in case of nerve root or spinal cord compression, and a neurosurgeon and/or orthopaedic surgeon should

To avoid undertreatment and overtreatment, expected survival is one of the major factors determining treatment selection in patients with symptomatic SBMs. Several studies have shown that the estimation of survival by clinicians in terminally ill patients is inaccurate and have suggested the use of prognostication models to prevent overtreatment or undertreatment [25e27]. Over the recent years, a multitude of such models have been developed, each consisting of a certain set of risk factors, most commonly the primary tumour, performance status and presence of visceral metastases. Patients are stratified according to their survival risk, and treatment can be adjusted accordingly. The accuracy of these models is reasonably good [28,29]. It is suggested to use one of the models proposed by Bartels [30], Van der Linden et al. [15] or Bollen et al. [10]. The model of Bartels et al. can be used online (http://ebh-research. ruhosting.nl/PredictionModel/). The Bollen model has also been adapted for use in patients with metastases to the long bones and is available in the App Store and Google Play store (search for ‘OPTIModel’). Owing to the improving life expectancies as a result of better systemic therapies, these models should be updated regularly.

7. Patient selection

7.2. Spinal stability and extent of SBMs Another factor in treatment selection is the stability of the spinal column. Especially in metastatic disease, this can often be difficult to assess. In 2010, the Spinal Oncology Study Group introduced the Spinal Instability

Table 2 Differential diagnosis for back or neck pain in a patient with a history of cancer. Clinical complaints

(Radiating) back or neck pain

Neurological deficit

Differential diagnosis

Osteoporotic spinal fracture (especially with long-term corticosteroid use) Hernia nuclei pulposi Spondylodiscitis or spondylitis (especially in immunocompromised patients) Tumour growth in the dorsal pleura Spondylosis (spondylarthrosis)

Leptomeningeal metastasis Radiation myelopathy (in irradiated patients) Bacterial/viral meningitis (especially in immunocompromised patients) Epidural abscess or haematoma (in spinal analgesia) Intramedullary metastasis Spinal lipomatosis (with long-term corticosteroid use) Benign tumour (e.g. meningioma or schwannoma) Arteriovenous malformation Primary bone tumour Transverse myelitis Sarcoidosis Multiple sclerosis

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Fig. 2. Flowchart of the diagnostic process. (A) See Table 1 for alarm symptoms. (B) Perform an MRI of the total spine, as soon as possible in case of suspected MESCC and within 24e48 h for progressive unilateral radicular symptoms. (C) Reason for doubt about the relationship with an already known tumour are an atypical MRI image, no progression of disease elsewhere, time interval >2 years in lung cancer and >5 years in other tumour types. (D) A recent PETeCT is necessary to map the extent of disease and/or to select a lesion that is more accessible for biopsy. (E) Preferably wait with corticosteroids as they can make the diagnosis of haematological malignancy impossible. In case of progressive deficit (despite corticosteroids), consider a decompressive surgery immediately. MRI, magnetic resonance imaging; MESCC, malignant epidural spinal cord compression; PETeCT, positron-emission tomographyecomputed tomography.

Neoplastic Score (SINS). It is a consensus-based guideline that aims to aid clinicians in the assessment of the spinal stability in neoplastic disease [31]. Based on the six criteria, the SINS classifies the spine as stable, potentially unstable or unstable and recommends surgical consultation for the latter two categories. Several

studies have shown that the SINS has substantial to excellent interobserver reliability [32e35]. However, it does not seem that the overall SINS score is predictive of the spinal instability [36e38], and its usefulness as a prognostic tool for surgical decision-making is limited. It is recommended to consult a spinal surgeon in all

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Fig. 3. Flowchart of patient and treatment selection. (A) Start with corticosteroids in case of clinical MESCC. Discuss treatment policy in a multidisciplinary setting. Start the treatment within 24 h in case of clinical MESCC, within 72 h in case of only radiological MESCC and within 14 days in case of only pain. (B) Assess survival using a prognostic model. A life expectancy of at least 6 months is required in case of combined surgical procedures. (C) Assess the chance of success with systemic therapy in case of a malignancy with a high probability of a rapid response. (D þ E) Consult a spinal surgeon to assess whether surgery is a viable option. (F) Consult a radiation oncologist to assess whether radiotherapy is a viable option. MESCC, malignant epidural spinal cord compression.

cases where there are clinical or radiological signs of spinal instability, and the SINS provides a good framework to do so. If more than three adjacent vertebral bodies are involved, surgery is frequently not recommended. The same holds true for multiple, extensive lesions within the spinal column. Treatment selection is summarised in the flowchart depicted in Fig. 3.

8. Treatment 8.1. Radiotherapy Treatment for SBMs will generally be palliative in nature and aimed at alleviating symptoms and achieving local control of the metastasis. Radiotherapy is considered the cornerstone of treatment, achieving a 60e80%

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decline in pain and improving neurologic symptoms in 10e90% of cases [39e43]. The major benefit is that it is non-invasive, and any side-effects are generally transient in nature and are well tolerated. Patients presenting with pain because of SBMs without signs of nerve root or spinal cord compression should be treated with a single fraction of 8 Gy. The use of fractionated schedules with higher doses does not increase the duration of response nor increase the percentage of pain reduction [39,44,45]. However, in case of solitary or oligometastatic disease, it is assumed that a more aggressive intervention (i.e. surgery or radiotherapy) might increase symptom-free survival or possibly provide cure [46]. Hence, in those cases, it is recommended using a dose of 30e39 Gy in 10e13 fractions or more advanced radiation techniques to allow the delivery of an ablative dose. For example, with stereotactic body radiotherapy (SBRT), very high doses can be applied to a small target volume, combined with a steep drop off of the dose gradient around the borders of the target to spare adjacent organs at risk. However, it remains to be demonstrated whether there are any higher response rates and less toxicity in comparison to conventional techniques [47]. Even though several articles have been published recently [64,65], it is still unclear whether the higher risk of vertebral compression fractures associated with SBRT and the higher costs weigh up to potentially faster and long-lasting clinical responses [66]. In an oligometastatic setting, however, the benefit of SBRT over conventional radiotherapy is clear, providing treatment with a curative, instead of palliative intent. If possible, patients treated with SBRT for SBMs should be enrolled in trials. Patients presenting with neurologic deficits and patients who are not candidates for surgical intervention can be treated with a single fraction of 8 Gy if they have a poor life expectancy or with a fractionated schedule of at least 30 Gy if their life expectancy is 6 months or more. Irradiation with a higher dose may lead to lower rates of reirradiation and recurrent symptomatic MESCC [48,49]. 8.2. Surgery Surgical techniques range from minimal invasive options to en bloc resection of the affected spinal segments. Vertebroplasty and kyphoplasty are percutaneous techniques where polymethylmethacrylate (PMMA) is injected in the vertebral body under X-ray or CT guidance. The injection of this ‘bone cement’ stabilises the vertebrae and reduces pain caused by microfractures and prevents further collapse of the vertebral body. In the case of a kyphoplasty, the height of a collapsed vertebra is restored by inflating a small balloon, before injecting PMMA in the created cavity. These techniques should not be used in the case of pain or neurologic

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deficit caused by nerve root or spinal cord compression as they do not reduce the tumour size. Retrospective studies have shown a reduction in pain in 74e100% of patients [50e52], and a complete response was seen in up to 31% of patients [53]. There are too few studies to demonstrate any clinical differences between vertebroplasty and kyphoplasty [54]. The most frequently reported complication is cement leakage, occurring in up to 75% of patients [55] and is usually asymptomatic. Low viscosity and a larger quantity of the injected PMMA and greater cortical destruction of the vertebra seem to increase the risk of cement leakage [50,56]. These techniques should not be used in the case of MESCC as this could lead to increased neurologic deficit. Radiofrequency ablation (RFA) is a percutaneous technique where a needle is inserted into the affected vertebral body, through which high-frequency radio waves are channelled, causing high temperatures resulting in necrosis. This procedure is often combined with a vertebroplasty to increase the mechanical stability. The effects of RFA with or without added vertebroplasty have been described in several smaller case series and are comparable to vertebroplasty alone [57e59]. Open techniques include decompressive surgery and corpectomies, which should be followed by fixation of the spinal column to ensure stability. A laminectomy without stabilisation is rarely indicated because of the high risk of creating instability. Intralesional piecemeal excisions or en bloc resections of the vertebral body require more extensive reconstructive surgery by means of expandable cages or allografts. No studies were found comparing the different types of open surgery and anterior or posterior approaches, with regard to functional outcomes, morbidity and mortality. Minimally invasive spinal surgery for metastases has been associated with a lower complication rate when compared with traditional open methods; however, this has not yet been confirmed in a comparative study. Therefore, no specific recommendations can be given on which surgical technique should be used in which case. Even though these techniques are highly effective in achieving local control and alleviating or preventing neurologic symptoms, the complication rate is high (20e37%) [60e62], and recovery from major surgery can be especially challenging in this patient population. Consequently, for performing these types of palliative operations, life expectancy of at least 3 months for minimally invasive procedures to 6 months for open combined surgical procedures is recommended. 8.3. Systemic therapy Systemic anticancer therapy can be used as a first choice in patients with certain tumours, if there is a high chance of a rapid effect (i.e. multiple myeloma, non-Hodgkin

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lymphoma (NHL) of high or intermediate malignancy, metastatic germ cell tumours, melanoma with BRAF mutation); or if there is a vital indication for chemotherapy owing to metastases elsewhere in the body that cannot be delayed or if there are no possibilities for radiotherapy or surgery.

stability. The indications for radiotherapy, surgery, systemic therapy and adjuvant treatments are also described. Based on the previously mentioned information, several recommendations can be made for the diagnostic process (summarised in Fig. 2) and the selection of an appropriate treatment (summarised in Fig. 3).

8.4. Other treatments Recommendations

Corticosteroids can be started in the case of symptomatic spinal cord compression as it reduces swelling and oedema around the spinal cord. A pain flare after radiotherapy can also respond well to steroids. The optimal dose is not quite clear, but generally 4e8 mg once daily is well tolerated. There is evidence that in case of MESCC without neurological deficit, omitting treatment with corticosteroids does not lead to a decreased likelihood of mobility after radiotherapy [67]. Bisphosphonates or denosumab can be prescribed to prevent further skeletal complications. Denosumab has been shown to be superior in preventing or delaying skeletal events without added risk of complication [63]. 9. Patient information and communication The treating physician should involve the patient and relatives when considering the selection of treatment and starting a treatment or not. Adverse events and complications of a treatment versus the estimated survival and improvement of the overall quality of life should be involved in this discussion. Given the possible severe complications of SBMs, cancer patients with known SBMs or a high risk of developing SBMs should be aware of the symptoms that require them to (urgently) contact their treating physician. For this purpose, an Appendix with alarm symptoms was created, along with the local contact data (see Appendix 1 of the guideline). Furthermore, as reliable information on SBMs is scarce, an extensive patient information sheet was drawn up about SBMs (see Appendix 2 of the guideline). 10. Summary and recommendations Recently, the Dutch evidence-based guideline on the management of SBMs was published. It provides an overview of the multidisciplinary approach to the diagnostic process and treatment of SBMs from solid tumours and spinal localisations of haematological malignancies. It focusses on a proactive approach in the prevention of pain and neurological symptoms, by providing clear indications on when to perform additional examinations and on how to select patients for specific treatments. This article summarises several aspects of this guideline, including clinical presentation with signs and symptoms, imaging and work-up as well as assessing the survival and

 Cancer patients and known SBMs or a high risk of developing SBMs should know what symptoms they need to be alert to and which care provider they can go to in case of these symptoms  Consider the presence of SBMs in patients with back pain, especially night pain, and a history of or currently active malignancy, especially in the presence of the symptoms described in Table 1.  An MRI is the modality of choice for assessing patients suspected of SBMs.  The duration and extent of neurological symptoms determine how rapidly an MRI should be obtained and treatment should commence.  Start corticosteroids as soon as possible (not interfering diagnosis) in case of neurological deficit.  If the primary tumour is unknown, consider performing a PETe CT and a biopsy of the spinal lesion.  Treatment selection should depend on symptoms, the extent of SBMs and expected survival. It is recommended to use a predictive model to assess survival.  Consider short-course radiotherapy and minimally invasive surgery in patients with a short life expectancy.  Patients with a longer expected survival are good candidates to undergo more extensive surgical procedures and radiotherapy regimens.  Systemic anticancer therapy can be used as a first choice for treating SBMs in patients with certain tumours, if there is a high chance of a rapid effect.  Consult a spinal surgeon in the case of suspected spinal instability. The SINS provides a framework to facilitate communication but is not predictive of the instability. SBMs, spinal bone metastases; MRI, magnetic resonance imaging; PETeCT, positron-emission tomographyecomputed tomography; SINS, Spinal Instability Neoplastic Score.

Conflict of interest statement None of the authors has any conflict of interest to declare. Funding This research did not receive any specific grant from funding agencies in the public, commercial or not-forprofit sectors.

Acknowledgements The authors want to thank A. van der Mei, MSc, (the Netherlands Comprehensive Cancer Organization

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[IKNL], Groningen, the Netherlands) and R. de Peuter, MSc, (the Netherlands Comprehensive Cancer Organization [IKNL], Utrecht, the Netherlands) for the secretarial support. They further acknowledge the advisors of the working group for their contribution to the development of ‘the Dutch national guideline on metastases and haematological malignancies localised within the spine, a multidisciplinary collaboration towards timely and proactive management’: W.C. Peul, MD, PhD, (Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands), W.C.H. Jacobs, PhD, (Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands), O. van der Hel, PhD, (the Netherlands Comprehensive Cancer Organization [IKNL], Rotterdam, the Netherlands). Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.ejca.2018.08.028.

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