Guideline sources The following summarized guidelines for the evaluation and management of Ewing's sarcoma (ES) are prepared by our editorial team based on guidelines from the European Reference Network on Genetic Tumour Risk Syndromes (GENTURIS/ERN PaedCan/EURACAN/ESMO 2021) and the National Comprehensive Cancer Network (NCCN 2021). 1 2 Calculator Calculator Calculat Eastern Cooperative Oncology G Karnofsky performance status s TNM cl Guidelines 1. Diagnostic investigations History and physical examination: As per ESMO 2021 guidelines, elicit medical history and perform physical examination in the initial work-up of patients with suspected primary bone sarcoma. B https://web.pathway.md/diseases/recK5pKn04x5UXoyE 1/4 6/29/23, 4:20 AM Ewing's sarcoma Pathway As per NCCN 2021 guidelines, elicit history and perform physical examination in patients presenting with suspected ES. B Imaging for staging: As per ESMO 2021 guidelines, obtain radiological assessment in the initial work-up of patients with suspected primary bone sarcoma. B Show 2 more As per NCCN 2021 guidelines: Obtain the following imaging modalities in the initial work-up of patients with ES: MRI +/- CT (both with contrast) of primary site chest CT positron emission tomography/CT (head-to-toe) and/or bone scan. B Consider obtaining screening MRI of spine and pelvis in the initial work-up of patients with ES. C Laboratory tests: As per ESMO 2021 guidelines, obtain baseline serum ALP and LDH in patients with ES. B As per NCCN 2021 guidelines, obtain LDH at presentation of patients with ES. B 2. Diagnostic procedures Biopsy and pathology: As per ESMO 2021 guidelines, perform biopsy in the initial work-op of patients with suspected primary bone sarcoma. B Show 6 more As per NCCN 2021 guidelines: Obtain cytogenetics and/or molecular testing (may require re-biopsy) in patients with ES. B Consider performing bone marrow biopsy in patients with ES. C 3. Medical management Setting of care: manage patients with bone sarcomas at reference centers and/or within reference networks able to provide access to the full spectrum of care and age-specific expertise. B Management of local/locoregional disease: As per ESMO 2021 guidelines, offer interval-compressed vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide as first-line therapy in patients with ES. B Show 6 more As per NCCN 2021 guidelines, offer the following local control options in patients with stable/improved disease following primary treatment: wide excision https://web.pathway.md/diseases/recK5pKn04x5UXoyE 2/4 6/29/23, 4:20 AM Ewing's sarcoma Pathway definitive radiotherapy and chemotherapy amputation in selected cases. B Show 7 more Management of advanced/metastatic disease: As per ESMO 2021 guidelines, offer chemotherapy in patients with metastatic disease at diagnosis similar to that used for localized disease. B Show 4 more As per NCCN 2021 guidelines, offer wide excision or definitive radiotherapy and chemotherapy for local control to primary site in patients with metastatic ES. B Show 7 more 4. Specific circumstances Patients with extraskeletal ES: Treat patients with extraskeletal ES following the same principles as for bone ES, incorporating chemotherapy in all patients and radiotherapy in most patients. B Decide on the number of chemotherapy cycles in patients with cutaneous/subcutaneous ES on an individual case basis, at a multidisciplinary level and with the patient. B 5. Patient education Fertility consultation: consider offering fertility consultation at initial presentation of patients with ES. C 6. Follow-up and surveillance Surveillance: As per ESMO 2021 guidelines, consider including the following in the follow-up of patients with high-grade bone sarcomas: physical examination cross-sectional imaging plain radiograph of the primary site CXR/chest CT. C Show 3 more As per NCCN 2021 guidelines, include the following in the surveillance of patients with stable/improved ES following primary treatment: physical examination MRI +/- CT (both with contrast of primary site) chest imaging (X-ray or CT) every 2-3 months radiographs of primary site CBC and other laboratory studies as indicated. B Show 2 more https://web.pathway.md/diseases/recK5pKn04x5UXoyE 3/4 6/29/23, 4:20 AM Ewing's sarcoma Pathway Management of relapse: As per ESMO 2021 guidelines, offer alkylating agents in combination with topoisomerase inhibitors, irinotecan with temozolomide, gemcitabine and docetaxel, high-dose ifosfamide or carboplatin with etoposide in patients with relapsed disease. B As per NCCN 2021 guidelines, offer the following options in patients with relapsed/refractory disease: initially stable/improved disease following primary treatment: chemotherapy +/- radiotherapy +/- without surgery progressive disease following primary and additional treatment: chemotherapy or best supportive care. B Show 2 more Clinical findings Patient demographics Symptoms Children Back pain White race Chest pain Cough Past medical history Dyspnea Fatigue Bone marrow metastasis Fever Lung metastasis Localized bone pain Lab findings Localized bone swelling Muscle weakness serum ALP Urinary retention serum LDH Weight loss Imaging findings Neurological exam Codman's triangle Sciatica Hair-on-end appearance Mottled bone lesion Hematological findings Multilayered periosteal reaction Anemia Osteolytic lesion References 1. S J Strauss, A M Frezza, N Abecassis et al. Bone sarcomas: ESMO EURACAN GENTURIS ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021 Dec;32 12 1520 1536. Open 2. J Sybil Biermann, Angela Hirbe, Warren Chow et al. Bone Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. NCCN. 2021 Oct 8. Open https://web.pathway.md/diseases/recK5pKn04x5UXoyE 4/4