Management of bone sarcoma: ESMO-EURACAN-GENTURIS-ERNPaedCan Guideline

Diagnosis, pathology and molecular biology

• The initial work-up of a suspected primary BS tumour should be carried out at a sarcoma reference centre, and should include medical history, physical examination, radiological assessment and biopsy.
• Pathological diagnosis should be made by a bone tumour expert dedicated pathologist according to the 2020 WHO classification and should be supported by ancillary investigations whenever relevant.
• For surgical specimens, tumour size and local extent of spread, site, status of surgical margins and percentage of pathological response to preoperative ChT should be described.

Staging and risk assessment

• General staging should be carried out to assess the extent of distant disease, including chest CT, bone scintigraphy and/or WB-MRI and and/or FDG-PET-CT/MRI as clinically indicated. Baseline serum analysis in ES and osteosarcoma should include AP and LDH.

Treatment

Osteosarcoma

• Low-grade central and parosteal osteosarcoma are malignancies with a low metastatic potential that should be treated by surgery alone.
• urative treatment of high-grade osteosarcoma consists of multimodal ChT and surgery.
• oxorubicin, cisplatin, HD-MTX and ifosfamide have anti-tumour activity in osteosarcoma [I, A]. In patients >40 years, preferred regimens combine doxorubicin, cisplatin and ifosfamide.
• igh-grade craniofacial osteosarcoma should be treated the same way as high-grade osteosarcoma of other sites [IV, B]. In this location, RT can be proposed when complete surgery is not feasible and in patients undergoing resection with positive margins.
• eavy-particle RT and IMRT can be considered, particularly for unresectable primary tumours.
• rimary metastatic osteosarcoma patients are treated with a curative intent following the same principles of non-metastatic osteosarcomas.
• he treatment of recurrent osteosarcoma is primarily surgical in the case of isolated lung metastases or local recurrence.
• RFA and stereotactic RT are potential alternative local treatment options in patients unfit for surgery and for small lung or bone metastases.
• Second-line ChT for recurrent osteosarcoma includes ifosfamide or cyclophosphamide, possibly in association with etoposide and/or carboplatin [III, B], and other active drugs including gemcitabine and docetaxel.

Ewing sarcoma

• Molecular confirmation is mandatory for the distinction between ES and other RCSs.
• The interval-compressed VDC/IE regimen is currently the preferred first-line treatment in ES.
• The use of BuMel could be considered for selected patients with poor response to VIDE induction ChT and/or tumour volume >200 ml.
• The role of high-dose ChT has not been evaluated with interval compressed VDC/IE. The selection of the most appropriate consolidation should take into account the ChT regimen received and the need for RT.
• Complete surgical excision, when feasible, rather than RT as a sole modality is regarded as the best modality of local tumour control.
• RT alone should be used if complete surgical excision is not possible and in primary sites where surgery will lead to unacceptable morbidity.
• Adjuvant RT (pre- or post-operative) is indicated where the originally involved tissues cannot be completely resected with adequate surgical margins, for large-volume tumors or poor histological response [IV, B]. It should be considered in patients with non-sacral pelvic ES regardless of surgical margins, tumour volume or histological response.
• Treatment of patients with extraskeletal ES follows the same principles as bone ES.
• For cutaneous/subcutaneous ES the number of ChT cycles should be discussed on an individual case basis.
• For patients with metastases at diagnosis, ChT is similar to that for localised disease.
• ChT regimens for relapsed disease include alkylating agents in combination with topoisomerase inhibitors, irinotecan with temozolomide, gemcitabine and docetaxel, high-dose ifosfamide or carboplatin with etoposide.