What are the treatment guidelines for Ewing sarcoma?

Updated: Jul 01, 2020
  • Author: Mrinal M Gounder, MD; Chief Editor: Edwin Choy, MD, PhD  more...
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NCCN recommendations for treatment of Ewing sarcoma are as follows [1] :

  • Enrollment in a clinical trial should be considered when available; in addition, whenever possible patients should be referred to a tertiary care center with expertise in sarcoma, for treatment by a multidisciplinary team

  • Multi-agent chemotherapy for at least 12 weeks followed by local control therapy and adjuvant treatment; longer duration of initial chemotherapy can be considered for patients with metastatic disease, based on response

  • Restaging following chemotherapy

NCCN category 1 recommendations for first-line (primary, neoadjuvant, and adjuvant) therapy are as follows [1] :

  • VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide)(preferred regimen)
  • VIDE (vincristine, ifosfamide, doxorubicin, and etoposide)

Recommended primary therapy for patients with metastatic disease at initial presentation is as follows [1] :

  • VDC/IE
  • VDC (vincristine, doxorubicin, and cyclophosphamide)
  • VAI (vincristine, doxorubicin [Adriamycin], and ifosfamide
  • VIDE

For second-line therapy in relapsed, refractory, or metastatic disease, preferred regimens are as follows:

  • Cyclophosphamide and topotecan
  • Irinotecan ± temozolomide ± vincristine
  • Ifosfamide (high dose) ± etoposide

For patients with stable or improved disease after restaging, the NCCN recommends the following [1] :

  • Wide excision or definitive radiation therapy with chemotherapy, or amputation in selected cases.

  • Postoperative chemotherapy for 28-49 weeks, depending on the type of regimen and the dosing schedule (category 1 for wide excision)

  • Postoperative radiation therapy in addition to chemotherapy if surgical margins are positive or very close

  • Surveillance with physical exams, laboratory tests, and imaging studies

  • If surveillance reveals progressive disease or relapse, chemotherapy with or without radiation therapy

For patients with progressive disease after primary treatment, the NCCN recommends considering radiation therapy and/or surgery to the primary site, followed by chemotherapy or best supportive care. 

For patients with metastatic Ewing sarcoma, the NCCN recommendations for local control therapy to primary site are as follows:

  • Wide excision with adjuvant chemotherapy, plus radiation therapy in cases of positive margins
  • Definitive radiation therapy and chemotherapy
  • For oligometastatic disease, resection of metastases or radiation therapy
  • For lung involvement only with partial response, resection plus whole-lung irradiation
  • For lung involvement only with complete response, consider whole-lung irradiation

For widely metastatic Ewing sarcoma, the NCCN recommends the following:

  • Continuing chemotherapy only with palliative surgery  or
  • ​Palliative radiation therapy to symptomatic areas  or
  • Other techniques for multiple metastases  

ESMO-PaedCan-EURACAN chemotherapy recommendations for treatment of Ewing sarcoma are as follows [2] :

  • Preferred chemotherapy options include doxorubicin, cyclophosphamide, ifosfamide, vincristine, dactinomycin, and etoposide; most active protocols are based on five- to six-drug combinations of these agents.
  • Current trials employ 3–6 cycles of initial combination chemotherapy after biopsy, followed by local therapy, and another 6–10 cycles of chemotherapy, usually given at 2- to 3-week intervals.
  • Dose-dense regimens (with interval compression) were associated with a positive outcome in pediatric and adolescent (< 18 years) patients.
  • Recent studies recommend the use of busulfan and melphalan for highly selected patients with poor response to induction chemotherapy and/or tumor volume > 200 mL.
  • For patients with metastases at diagnosis, the chemotherapy regimen is similar to that for localized disease, but responses are less durable and patients have a worse prognosis.
  • Chemotherapy regimens for relapsed ES are not standardized. They include alkylating agents (cyclophosphamide and high-dose ifosfamide) in combination with topoisomerase inhibitors (etoposide and topotecan), irinotecan with temozolomide or gemcitabine and docetaxel, or high-dose ifosfamide or carboplatin with etoposide.

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