Spinal tumours: recommendations of the Polish Society of Spine Surgery, the Polish Society of Oncology, the Polish Society of Neurosurgeons, the Polish Society of Oncologic Surgery, the Polish Society of Oncologic Radiotherapy, and the Polish Society of Orthopaedics and Traumatology

The purpose of these recommendations is to spread the available evidence for evaluating and managing spinal tumours among clinicians who encounter such entities. The recommendations were developed by members of the Development Recommendations Group representing seven stakeholder scientific societies and organizations of specialists involved in various forms of care for patients with spinal tumours in Poland. The recommendations are based on data yielded from systematic reviews of the literature identified through electronic database searches. The strength of the recommendations was graded according to the North American Spine Society’s grades of recommendation for summaries or reviews of studies. The recommendation group developed 89 level A-C recommendations and a supplementary list of institutions able to manage primary malignant spinal tumours, namely, spinal sarcomas, at the expert level. This list, further called an appendix, helps clinicians who encounter spinal tumours refer patients with suspected spinal sarcoma or chordoma for pathological diagnosis, surgery and radiosurgery. The list constitutes a basis of the network of expertise for the management of primary malignant spinal tumours and should be understood as a communication network of specialists involved in the care of primary spinal malignancies. The developed recommendations together with the national network of expertise should optimize the management of patients with spinal tumours, especially rare malignancies, and optimize their referral and allocation within the Polish national health service system.


Introduction
Initially, the only purpose of our project was to develop recommendations for the evaluation and management of spinal tumours among clinicians caring for such entities. To the best of our knowledge, no comprehensive recommendations regarding the full spectrum of spinal tumours have been published thus far. Soon after starting the project, we added another goal: the development of a network of expertise at a national level for the management of primary malignant spinal tumours in Poland with a plan to incorporate this network into the existing organizational structure of the Polish national cancer care system. Such a network will follow recommendations of the European Union Joint Action on Cancer and the European Partnership for Action Against Cancer (EPAAC) [1].

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The EPAAC recommends the establishment of networks of expertise in the management of soft tissue and bone sarcomas in regions where it is not possible to establish comprehensive centres for their management. In Poland, similar to the majority of other countries, such centres offering comprehensive expertise under the one roof do not exist or are very rare. Our expertise network seems to be a reasonable alternative given the lack of such centres and a good response to the EPAAC recommendations.
We believe that with the national expertise network, our recommendations have an increased chance to be fully met in everyday clinical practice.
Incorporation of our expertise network into the existing national system of cancer care in Poland should be straightforward. This is because in Poland, interdisciplinarity in the management of cancer is a fundamental principle and a statutory requirement of a Polish national cancer care system. This principle is executed with relative ease for most oncology patients in Poland, but clinicians and patients can experience problems in regard to very rare malignancies, such as spinal sarcomas and chordomas. Access to the expertise network for both patients and clinicians encountering spinal tumours should complement the Polish cancer care system in the management of rare primary spinal malignancies. Currently, specialists with expertise in these tumours are dispersed across the country and, consequently, problems with coordinated referral and interdisciplinary management of these patients exist. In practice, interdisciplinary services for the management of rare spinal tumours are not available under the one roof, even at quaternary or university hospitals. Furthermore, the interdisciplinary management of these tumours may not be available, even within a single broader region of the country. Complex oncologic spine surgery can be performed by a specialist in one corner of the country, molecular histology of sarcomas in another corner, and proton beam therapy or radiosurgery in yet another corner. Similar dispersions of expertise and facilities for the management of rare malignancies can be found worldwide, including in highly developed countries. We believe that a dedicated expertise network for rare spinal tumours at the national level will improve the coordinated interdisciplinary management of patients, despite the dispersion of experts and facilities across the country.

The recommendations development group
The project to develop such recommendations was an initiative of the Executive Committee of the Polish Society of Spine Surgery. The Committee invited some stakeholder organizations to the project to ensure broad representation

Grading recommendations and level of evidence
The recommendations were based on systematic reviews of the literature identified from searching electronic databases. The strength of the recommendations was graded according to the North American Spine Society's Grades of Recommendation for Summaries or Reviews of Studies (Tables 1  and 2). A: good evidence (level I studies with consistent findings) for or against recommending intervention; B: fair evidence (level II or III studies with consistent findings) for or against recommending intervention; C: poor quality evidence (level IV or V studies) for or against recommending intervention; and I: insufficient or conflicting evidence not allowing for a recommendation for or against intervention [2,3].
Each identified source of evidence was rated in terms of the strength of yielded evidence with the use of levels of evidence for primary research questions as adopted by the North American Spine Society in January 2005 and other societies and journals, namely, the American Academy of Orthopaedic Surgeons, Pediatric Orthopaedic Society of North America, Clinical, Orthopaedics and Related Research, Journal of Bone and Joint Surgery and Spine (Table 2) [3].

Formulation of recommendations
All members of the Recommendation Development Group participated in the recommendation development process. Each team proposed preliminary recommendations in a structured way that included formulating the recommendation and the following: (1) classifying the strength of the formulated recommendation, (2) classifying the quality of the study that the recommendation was based on, (3) referencing the source of the study, and (4) stating the type of the study, e.g., randomized controlled trial, retrospective study, and expert opinion. The preliminary recommendations were summarized in a table by each working team (Table 3). Tables with preliminary recommendations from all working teams were compiled into one table embedded in a Word file that was available online for all members of the Recommendation Development Group. The teams were asked to review the table and provide written remarks, comments, objections or opinions in the comments panel of the Word file based on their areas of expertise. This process was supervised by four chairs who were members of the development group but were not involved in the literature search and instead chaired all the meetings and voting sessions of the group. Once the preliminary recommendations were reviewed, each single recommendation was separately subjected to voting during a series of meetings of the whole Recommendation Development Group. Every single preliminary recommendation was separately accepted as a final recommendation when at least 75% of members voted positively. Recommendations that did not achieve this result during the first round of voting were returned to the appropriate working team for revision. Based on the revision, the recommendation could be either rejected or reformulated by the working team and subjected to the second review and vote by the whole Development Group during the subsequent meetings. Those preliminary recommendations that were not accepted during a second vote were ultimately rejected or when representing a crucial issue, put on a discrepancy list.

Expertise network for multidisciplinary management of rare primary spinal tumours
Based on internal surveys in the stakeholder societies represented in the development group, we created a list of institutions, hospitals, teams and individual colleagues with expertise in the diagnosis and treatment of rare malignant spinal tumours. Specifically, we inquired about facilities offering in-depth molecular histological diagnostics, stereotactic body radiation therapy of the spine, proton beam therapy, and complex oncologic spine surgery. Each scientific society was asked to provide such a list with regard to its specialties. A survey among the members of the Polish Society of Spine Surgery concerning their experience in complex oncologic spine surgery, namely, en bloc Enneking-appropriate resections, allowed us to create a list of centres and individual Level I high-quality randomized controlled trial (RCT) with statistically significant differences or no statistically significant differences but narrow confidence intervals, systematic review of level I RCTs (with homogenous study results) Level II lower-quality RCT (e.g., < 80% follow-up, no blinding, or improper randomization), prospective comparative study, systematic review of level II studies or level 1 studies with inconsistent results Level III case control study, retrospective comparative study, systematic review of level III studies Level IV case series Level V expert opinion colleagues who have expertise in this type of surgery. These experts were also asked about their willingness and readiness to accept patients requiring this type of surgery from other institutions/colleagues on a regular basis.

Results
Eighty-nine recommendations were developed and accepted by the Recommendation Development Group and divided into four sections: (1) diagnostics, (2) primary tumours, (3) metastatic tumours, and (4) discrepancies (Tables 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27 respectively). The list of recommendations will be available on the homepages of stakeholder organizations participating in the development of recommendations and accompanied by an appendix including a list of institutions, teams and individual specialists with expertise in the diagnostics and management of rare primary malignant tumours to optimize patient referral and allocation within the cancer care system of Poland (Table 28).

Discussion
As mentioned above, interdisciplinarity in the management of cancer is a fundamental principle and a statutory requirement of the Polish national cancer care system.
While the principle of interdisciplinarity in the management of most spinal tumours is relatively easy to execute, this is not the case for primary malignant spinal tumours requiring sophisticated molecular diagnostics as well as complex oncologic spine surgery.
No single centre in Poland provides complete management of rare primary malignant spinal tumours from indepth molecular histological diagnosis through complex oncologic spine surgery to spine radiosurgery and chemotherapy in one institution.
Currently, patients with such tumours and some clinicians involved in the care of such patients may not be aware of the centres offering unique molecular diagnosis or top-level oncologic surgical treatment of the spine. With the dispersion of these highly specialized services across Poland, it may take time and effort to find an institution with the required facilities. A patient may undergo surgical treatment in one place and radiotherapy or chemotherapy in another, while having molecular diagnosis done in yet another place. In everyday practice, such patients and clinicians may both feel lost in regard to deciding which referral centre can offer the most appropriate diagnostics and treatment. Based on internal surveys within scientific societies represented in the development group, we prepared a list of institutions and colleagues with expertise  Table 1) Reference to the source of evidence (journal articles, textbooks, etc.) To be chosen from five possible options I-V (see Table 2) To be chosen from the following: RCT, systematic reviews, prospective studies, retrospective studies, case series, expert opinions 1 3 in the diagnosis and treatment of rare malignant spinal tumours, namely sarcomas and chordomas. The list will be available as an appendix to the recommendations on the homepages of the stakeholder organizations. The list aims to give clinicians involved in the care of patients with spinal tumours clues on where to refer patients with rare spinal malignancies for optimal management, especially in regard to complex oncologic spine surgery. The colleagues experienced in this type of surgery declared they would be ready to accept such cases on a regular basis. The appendix will also include a list of institutions with expertise in performing molecular pathology of sarcomas and a list of places and colleagues providing radiosurgery. Therefore, we recommend referring patients with primary malignant tumours to these centres or colleagues. This approach should not be a problem, as in Poland, allocation and free Radiology reports should include the spinal instability neoplastic score (SINS) in patients with neoplastic disease of the spine Among radiation oncologists, SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumour-related spinal disease: is the spine 'stable' or is there a 'current or possible instability' that warrants surgical assessment? I [12] V Multicentre validation study referrals to any institution within the Polish national health service system are protected by the patients' right to freely choose primary care doctors, specialists, hospitals, and medical institutions anywhere in the country. Free referrals within the system are by no means restricted, and patients, regardless of their place of residence in Poland, who are entitled to free services of the national health system (NHS) have the freedom to choose the place and physician for treatment. Additionally, we believe that the allocation of patients with spinal sarcomas and chordomas to  We recommend 1 That medical centres that perform diagnostic and therapeutic procedures on spine sarcomas should have the following organizational possibilities: (1) Staff: oncological surgery specialist/orthopaedist and neurosurgeon with experience in en bloc spine surgery/paediatric surgeon with experience in the treatment of bone sarcomas-on site, clinical oncology specialist-on site, radiotherapy specialist-on site, physiotherapist-on site, psycho-oncologist-at the location (2) Intensive care unit-on site (3) Radiology laboratory (24/7 access)-USG, CT, MRI in a location with the possibility of performing an intraoperative X-ray examination (4) Histopathology laboratory with the possibility of performing an intraoperative examination pathology at the location (5) Possibility of a multidisciplinary consultation (oncologist/orthopaedic surgeon, radiotherapist, clinical oncologist-chemotherapist, pathologist, radiologist) at the centre (6) Possibility of carrying out adjuvant treatment (chemotherapy, radiotherapy with the possibility of IMRT and stereotaxic techniques) at the location or under an agreement with an external centre. Coordination of systemic treatment and radiotherapy must be ensured (7) Possibility to perform cytogenetic and molecular diagnostics-at the location or on the basis of an agreement with an external centre (8) In Poland, it is recommended that patients with bone sarcomas be treated only in specialized reference centres or in units with extensive experience in treating patients with this cancer, where at least 20-25 patients with bone sarcomas are treated annually Biopsy be performed in a centre with full surgical and pathomorphological facilities The accuracy of the biopsy is influenced by the experience of the surgeon performing the procedure and the pathologist assessing the bone tissue, therefore the biopsy should be performed in a centre with full surgical and pathomorphological facilities. Errors, complications, and changes in the course and outcome are two to twelve times greater when the biopsy is done in a referring institution instead of in a treatment centre B [20,21] III Retrospective the recommended centres will not burden colleagues with expertise in oncologic spine surgery, and it is unlikely that these surgeons will be swamped by these additional cases, as these tumours are extremely rare. With the incidence of spinal sarcomas being 0,19-0,38 per 1,000,000 people, only approximately 7-15 new cases can be expected in Poland per year. The slightly higher incidence of spinal chordoma, 1 per 1,000,000 population, means approximately 38 new cases can be expected in Poland [22][23][24]. The list is not intended to mandate referrals to the recommended places and specialists, especially in regard to surgical management. Additionally, these specialists will not be obliged to accept such referrals. The estimated number of yearly referrals for spinal sarcomas and chordomas should not exceed 50. Thus, even if only a dozen colleagues have expertise in oncologic spine surgery, each one would potentially accept no more than 3-5 cases if the allocation is evenly distributed across the country. These colleagues declared that they are happy to accept such referrals. Conversely, colleagues who did not declare expertise in complex oncologic spine surgery but will eventually gain such skills with increasing experience should not feel an obligation to refer spinal sarcoma/chordoma patients to colleagues renowned for their expertise in oncologic spine surgery. We understand that complex oncologic spine surgery follows the principles of the Weinstein-Boriani-Biagini (WBB) surgical system used for planning en bloc resections of spinal tumours [25][26][27]. The WBB systems were developed based on the Enneking principles of four types of surgical margins for musculoskeletal sarcoma [28]. Some may confuse true extralesional en bloc resection according to the WBB/ Enneking principles with Tomita's en bloc spondylectomy, which is excision of the whole vertebra in two pieces from the spine, with the cut line dividing the vertebra into two pieces running through the pedicles [29]. An increasing number of colleagues performing spine surgery are skilled in these techniques and apply them for nonneoplastic pathologies of the spine, such as spinal deformities or infections [30,31]. These skills do not necessarily translate into expertise in truly extralesional resections because the latter may require different combinations of surgical strategies, including combinations of two, three or even more separate routes of surgical access. Only a few colleagues among spine surgeons have expertise in this type of spine surgery due to the extreme rarity of primary malignant spinal tumours. The chance that an average spine surgeon will encounter a patient with spinal sarcoma or chordoma during his or her career is minimal. The majority of excellent spine surgeons will never    operate on such spinal tumours, except of a few colleagues specializing in complex oncological spine surgery. Our recommendation for Enneking's wide and marginal excision of spinal sarcomas and chordomas implies that surgical treatment should ideally be performed by surgeons with expertise in oncological spine surgery. This in turn imposes that a biopsy be performed by the surgeon operating on the tumour because the biopsy must be performed with the surgery plan in mind, as the biopsy tract will have to be removed en bloc with the tumour. Similarly, we recommend that the histopathological diagnostics of spine lesions suspected to be a primary malignancy be performed in recommended centres with expertise in malignant bone tumours. The list of such centres where a sample can be sent for evaluation as well as instructions on how to maintain and fix the biopsied sample will be included in the appendix to our recommendations. Malignant spinal tumours, in particular sarcomas, provide a particular diagnostic dilemma due to their variety, with more than 100 histological subtypes that often correspond to different biological behaviours and eventually respond differently to chemotherapeutic agents as well as targeted therapy and immunotherapy [32]. This heterogeneity in classification is accompanied by a broad spectrum of biological behaviour, from locally aggressive and nonmetastatic tumours to tumours that behave relatively indolently in the metastatic state to those that are highly aggressive and rapidly metastasise. Histological evaluations of sarcomas require advanced molecular diagnostics [32,33].      Advanced molecular diagnostics of rare musculoskeletal tumours, especially sarcomas, are available in very few places dispersed across Poland. This is also the case in other European countries, as documented by the EPAAC through an assessment of the quality of cancer care in Europe [1]. That is why in many countries, there is a trend to concentrate expertise for certain tumour types, including sarcomas, in dedicated centres or units [1].
In Poland, there is a Department of Soft Tissue, Bone Sarcoma and Melanoma at the Maria Sklodowska-Curie Institute Oncology Centre in Warsaw dedicated to the complex management of sarcomas. This department covers the majority of sarcoma cases in regard to molecular diagnostics and surgical treatment in Poland. However, the department mostly encounters only appendicular sarcomas, while spinal sarcomas are randomly operated on elsewhere across the country, often without a preceding biopsy or even radiological diagnosis or radiological suspicion of sarcoma. Therefore, most if not all spinal sarcomas are not operated on compliantly with the WBB/Enneking principles of extralesional excision. Once the preliminary histology of the operated spinal tumour confirms or suggests sarcoma, the sample may be sent for further in-depth diagnosis to another institution with better facilities and expertise in molecular pathology. Sometimes the sample may circulate from institution to institution before it reaches one that eventually establishes a thorough molecular diagnosis. To ensure a timely histological diagnosis and prevent patients from receiving an incomplete diagnosis of sarcoma, we identified all institutions and colleagues in Poland with expertise in molecular pathology techniques for sarcomas. These institutions will be listed in the appendix to the recommendations. Although few exist in the country, these institutions are able to cover the histological diagnostics of all spinal and appendicular sarcomas occurring in Poland. The EPAAC expert group recommends that for an institution to be considered a sarcoma centre, it should treat at least 100 new sarcoma patients (both soft tissue and bone) per year [1]. Similarly, guidance from the National Institute for Health and Care Excellence (NICE) in England and Wales states that multidisciplinary teams (MDTs) managing either soft tissue sarcoma or bone sarcoma should manage the care of at least 100 new patients per year (100 soft tissue and 50 bone sarcomas if the MDT manages both types) [34].   Therefore, we recommend sending biopsied and intraoperative samples suspected of being spinal sarcoma to the institutions listed in the appendix. This is in accordance with the recommendation of the European Cancer Organization (ECCO) expert group, who stresses that a diagnosis must only be made in dedicated sarcoma centres [1]. In addition, we added instructions to the appendix on how samples from tumours suspected to be a sarcoma should be fixed immediately after harvesting in the operating room.
Only two recommendations were placed on the discrepancy list (Table 28). These recommendations refer to emergency/urgent decompression of the spinal canal to counteract irreversible neurologic deficits in cases where no histological diagnosis was obtained. As everyday practice proves, emergency decompression surgeries are not uncommon in spinal tumours. Urgent or emergency decompression does not conflict with the principles of treatment of spinal tumours as long as the tumour is a metastasis. However, such decompression may conflict with the treatment principles when a tumour appears to be a primary tumour, especially haematopoietic tumours. Surgical treatment of haematopoietic tumours has no proven benefit compared with medical treatment, which usually provides excellent long-term outcomes. The view of some medical colleagues in the group clashed with the views of surgical colleagues. The first view stressed that surgery on haematopoietic malignancies of the spine can reduce or even deprive patients of a chance for a complete cure, even if adequate medical treatment is continued after the operation. The second view noted the impact of permanent complete or severe neurological deficits on quality of life, even if the patient receives stateof-the-art medical treatment. Whether patients with spinal tumours and a risk of permanent neurological deficit should undergo surgery without a biopsy should be discussed with the patient.
The majority of recommendations developed were graded as B and C, while the levels of the identified sources of evidence received grades of II-III, especially in regard to primary malignant spinal tumours. The rarity of these tumours is responsible for the paucity of data regarding their management and lack of higher levels of evidence usually achieved through high-quality therapeutic studies including larger numbers of analysed patients.

Conclusions
The developed recommendations together with the national network of expertise should optimize the management of patients with spinal tumours, especially those with rare malignancies, and optimize their referral and allocation within the Polish NHS.

Conflict of interest
The authors have no financial interests that are directly or indirectly related to the work submitted for publication.
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