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Malignant Bone Tumors (Other Than Ewing’S): Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up by Spanish Group for Research on Sarcomas (GEIS)

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Malignant Bone Tumors (Other Than Ewing’S): Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up by Spanish Group for Research on Sarcomas (GEIS) Cancer Chemother Pharmacol DOI 10.1007/s00280-017-3436-0 ORIGINAL ARTICLE Malignant bone tumors (other than Ewing’s): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS) Andrés Redondo1 · Silvia Bagué2 · Daniel Bernabeu1 · Eduardo Ortiz-Cruz1 · Claudia Valverde3 · Rosa Alvarez4 · Javier Martinez-Trufero5 · Jose A. Lopez-Martin6 · Raquel Correa7 · Josefina Cruz8 · Antonio Lopez-Pousa9 · Aurelio Santos10 · Xavier García del Muro11 · Javier Martin-Broto10 Received: 7 July 2017 / Accepted: 15 September 2017 © The Author(s) 2017. This article is an open access publication Abstract Primary malignant bone tumors are uncommon of a localized bone tumor, with various techniques available and heterogeneous malignancies. This document is a guide- depending on the histologic type, grade and location of the line developed by the Spanish Group for Research on Sar- tumor. Chemotherapy plays an important role in some che- coma with the participation of different specialists involved mosensitive subtypes (such as high-grade osteosarcoma). in the diagnosis and treatment of bone sarcomas. The aim is In other subtypes, historically considered chemoresistant to provide practical recommendations with the intention of (such as chordoma or giant cell tumor of bone), new targeted helping in the clinical decision-making process. The diag- therapies have emerged recently, with a very significant effi- nosis and treatment of bone tumors requires a multidiscipli- cacy in the case of denosumab. Radiation therapy is usually nary approach, involving as a minimum pathologists, radi- necessary in the treatment of chordoma and sometimes of ologists, surgeons, and radiation and medical oncologists. other bone tumors. Early referral to a specialist center could improve patients’ survival. The multidisciplinary management of osteosar- Keywords Bone tumors · Bone sarcomas · Clinical coma, chondrosarcoma, chordoma, giant cell tumor of bone guideline · Diagnosis · Treatment and other rare bone tumors is reviewed in this guideline. Ewing’s sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic Introduction features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the Primary bone tumors are an uncommon and heterogeneous available data. Surgical excision is the mainstay of treatment group of malignancies. Osteosarcoma is the most frequent with 7 * Andrés Redondo Hospital Virgen de la Victoria, Campus de Teatinos s/nº, [email protected] 29010 Málaga, Spain 8 1 Hospital Universitario de Canarias, Carretera de Ofra s/n, Hospital La Paz, Paseo Castellama, 261, 28046 Madrid, 38320 San Cristóbal de la Laguna, Santa Cruz De Tenerife, Spain Spain 2 Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí, 9 Hospital de la Santa Creu i Sant Pau, C/. Mas Casanovas, 90, 89, 08026 Barcelona, Spain 08041 Barcelona, Spain 3 Hospital Vall d’Hebrón, Passeig de la Vall d’Hebrón 10 Hospital Virgen del Rocío, Av Manuel Siurot s/n, 119-129, 08035 Barcelona, Spain 41013 Sevilla, Spain 4 Hospital Gregorio Marañón, C/ Dr Esquerdo 46, 11 Institut Catalá d’Oncologia Hospitalet, Avinguda de la 28007 Marid, Spain GranVia de l´Hospitalet 199-203, L´Hospitalet de Llobregat, 5 Hospital Miguel Servet, Paseo Isabel la Católica 1-3, Barcelona, Spain 50009 Zaragoza, Spain 6 Hospital 12 de Octubre, Ctra, Andalucía, km. 5.4, 28041 Madrid, Spain Vol.:(0123456789)1 3 Cancer Chemother Pharmacol an estimated incidence average of 0.2–0.3 cases per 100,000 such as Magnetic Resonance Imaging (MRI), plain film per year in Europe. It occurs mainly in adolescents and young continues to offer canonical elements in the diagnostic adults, but is also seen in older patients, usually related to prior process of bone tumors [3]. radiotherapy or Paget’s disease. Chondrosarcoma is the most MRI is the next imaging step which allows both, a nar- frequent bone sarcoma in adults, with an incidence average of rower differential diagnosis and local staging. The imaging 0.2 cases per 100,000 per year. It often has an aggressive local protocol should include sequences T1-Spin-Echo (SE) and behavior but rarely metastasizing, although in some cases more T2-Fast-SE (FSE) weighted images (WI) with chemical fat aggressive forms can also be seen. Chordoma is a very uncom- suppression (FS) in the axial plane and in sagittal or coro- mon primary tumor of bone with invasive local behavior and nal planes. Short-TI Inversion Recovery (STIR) sequences metastatic potential, mostly after multiple local recurrences. also allow good T2 contrast, and they are recommended Giant cell tumor of bone (GCTB) is a rare tumor, affecting when susceptibility artifacts are present, in at least one mainly young adults. Although often considered benign, in plane. some cases it can metastasize and/or suffer malignant trans- MRI is also the main tool for local staging of primary formation. Lastly, Ewing’s sarcoma is a tumor of children and bone tumors and some important rules should be borne in adolescents that because of its specific biological, clinical and mind when it is performed, before any treatment: (a) it must therapeutic features will be the focus of a different guideline. include, at some point in the process, the two joints either Due to the complexity and rarity of bone tumors, Spanish side of the tumor in the coronal plane; (b) careful attention Group for Research on Sarcoma (GEIS) decided to develop should be paid to any epiphyseal or articular invasion, espe- this clinical guideline with the aim of providing practical cially in young patients without physeal closure; (c) STIR recommendations to help in the clinical decision-making sequences should not be used to measure tumor extension, process and improve outcomes for bone sarcoma patients. since they can lead to overestimation in both intramedullary Diagnosis and treatment of bone tumors requires a mul- and soft tissue (IV, A); (d) it is desirable that any follow- tidisciplinary approach, involving as a minimum patholo- up with MRI uses the same protocol every time, as it will gists, radiologists, surgeons, and radiation and medical enable a better comparison between them (IV, B). oncologists. There is a great deal of evidence demonstrat- Use of gadolinium contrast enhancement, static (CE- ing that early recognition and referral to a specialist center MRI) or dynamic (DCE-MRI), in diagnosis and evalua- that provides a multidisciplinary diagnosis and therapeu- tion of bone tumor is controversial, but it has two potential tic approach, and manages a high number of cases annu- advantages: (a) it allows adequate planning of biopsy route ally, could improve outcomes in patients with bone tumors. avoiding necrotic, hemorrhagic or low-grade sarcoma areas, Therefore, centralized referral should ideally be done from and (b) it allows monitoring of the response to chemother- the moment a diagnosis of a bone sarcoma is suspected (III, apy (IV, B). CE-MRI study requires an axial or coronal pre- A) [1]. contrast T1-SE WI with fat suppression (FS) sequence and the same after contrast. New MR diffusion-weighted images Methods (MR-DWI) have become increasingly used in the evaluation, staging and follow-up of bone sarcomas [4]. These guidelines have been developed by a multidisciplinary Neither MR-DWI nor DCE-MRI have demonstrated any panel of specialists in the different fields involved in the benefit for diagnostic purposes but there is some evidence of diagnosis and treatment of bone tumors. A bibliographic promising use when applied to response evaluation of neo- search of published articles was performed in the PubMed adjuvant therapies (mainly DCE-MRI) and for tumor staging database. In a face-to-face consensus meeting, each section and follow-up, as well as for searching for local recurrences was presented by one expert to the entire group, for a discus- or metastases other than lungs (mainly MR-DWI) (IV, B). sion and consensus of the statements. The panel adopted the To make the most of these procedures, they should be per- American Society of Clinical Oncology (ASCO) levels of formed at the time of basal protocol. evidence/grades of recommendation [2]. Computed tomography (CT) of the primary bone tumor is not always necessary for diagnosis, but CT can help in some instances to evaluate bone matrix or calcifications, especially Diagnosis and staging when chondroid tumors are suspected, or in chordoma (IV, A). Additionally, CT can be of value for planning surgery in Imaging complex areas like pelvis or spine (V, A). The key imaging diagnostic elements to analyze at baseline are summarized The initial approach to any suspected bone lesion must in Table 1. be with radiographic plain films taken in two orthogonal The radiological appearance of primary bone tumors can planes. In spite of more sophisticated imaging technologies be summarized as follows: 1 3 Cancer Chemother Pharmacol • Osteosarcoma usually shows a characteristic destructive invasion in juxtacortical variants, because of its surgical lesion in the metaphyseal area of long bones, mainly implications. around the knee, proximal humerus or proximal femur. • Chondrosarcoma should be considered anytime there is Mixed sclerotic or blastic matrix, and aggressive peri- a lytic, destructive lesion with amorphous, snowflake osteal reaction (‘hair-on-end’ or ‘Codman’s triangle’) are calcification, and mild or absent periosteal reaction in common features in 75% of cases of conventional cen- a patient over the age of 40. MRI helps to identify car- tral osteosarcoma. Other histological subtypes can show tilage tissue with its typical lobular or ‘grape’ pattern quite different patterns, such as: (1) pure lytic lesions in on T2-SEFSWI and rim enhancement in CE-MRI. Dif- telangiectatic osteosarcoma (frequently associated with ferential diagnosis between enchondroma and low-grade fluid–fluid levels on MRI) or in fibroblastic subtypes5 [ ]; chondrosarcoma needs a careful evaluation of clinical (2) a solid bone mass growing from the superficial cortex and radiological signs, but it is always challenging [6].
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