Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up ☆

Primary bone sarcomas (BSs) account for <0.2% of malignant neoplasms across all ages. The overall incidence rate ranges between 0.8 and 0.9 cases per 100 000/year, with single BS types having no more than 0.3 incident cases per 100 000/year. Osteosarcoma and Ewing sarcoma (ES) have a relatively high incidence in the second decade of life, whereas conventional chondrosarcomas are more common in older age. Osteosarcoma is the most common BS (incidence: 0.3/100 000/year). The incidence is higher in adolescents (0.8-1.1/100 000/year at age 15-19 years) but there is a significant second peak in the seventh and eighth decades of life. The male to female ratio is 1.4 : 1. In younger patients, most osteosarcomas arise in extremities, whereas the proportion of axial tumour sites increases with age. Risk factors for the occurrence of osteosarcoma include previous radiotherapy (RT), Paget disease of the bone and germline genetic abnormalities associated with Li–Fraumeni syndrome, Werner syndrome, Rothmund–Thomson syndrome, Bloom syndrome and hereditary retinoblastoma. ES is a round cell sarcoma (RCS) marked by a gene fusion involving a member of the FET family and a member of the ETS family of transcription factors. ES is the third most common BS (incidence: ∼0.1/100 000/year) and occurs most frequently in children and adolescents but is also seen in adults. Median age at diagnosis is 15 years and there is a male predominance. The most common ES primary sites are the extremity bones (50%), followed by pelvis, ribs and vertebrae. Any bone can potentially be affected, however, a soft tissue origin is also possible, especially in adults (30% of cases). ES is currently regarded as distinct from rarer and recently identified entities such as RCS with EWSR1 non-ETS fusions, CIC-rearranged sarcomas and sarcomas with BCOR alteration.4 Among RCSs with EWSR1 non-ETS fusions, EWSR1-NFATC2 is the commonest, has a strong male predominance, affects an older population and occurs mainly in bone. CIC-rearranged sarcomas mostly arise from soft tissues and are rare in bone. Among RCSs with BCOR alterations, the BCOR-CCNB3 variant occurs mainly in the bones and predominantly affects paediatric patients, whereas BCOR with internal tandem duplication has been described in soft tissue tumours of infancy. Conventional chondrosarcoma is the most frequent BS of adulthood (incidence: ∼0.2/100 000/year), with a median age at diagnosis between 30 and 60 years and no gender predominance.1 Dedifferentiated chondrosarcoma (DCS), mesenchymal chondrosarcoma (MCS) and clear-cell chondrosarcoma are ultra-rare chondrosarcoma subtypes, with an incidence of <0.1/100 000/year. Extraskeletal myxoid chondrosarcoma, although originally thought to be a cartilaginous neoplasm, does not show cartilage differentiation and is classified as a mesenchymal tumour of uncertain differentiation. This is covered by the European Society for Medical Oncology-European Reference Network for Rare Adult Solid Cancers-European Reference Network for Genetic Tumour Risk Syndromes (ESMO-EURACAN-GENTURIS) Clinical Practice Guideline (CPG) on soft tissue sarcomas (STSs). Conventional chordomas are even rarer than other types of BS, with an incidence of approximately 0.08/100 000/year and a median age at diagnosis of 60 years. There is a slight male predominance. Dedifferentiated and poorly differentiated chordomas are ultra-rare subtypes. Giant cell tumour of bone (GCTB) is locally aggressive, rarely metastasising and represents 5% of primary bone tumours, with an incidence of ∼1/1 000 000/year. High-grade spindle/pleomorphic sarcomas of bone are a heterogeneous group of primary malignant bone tumours that do not fulfil the histological criteria for a diagnosis of osteosarcoma, chondrosarcoma or ES.