The Ewing family of tumors. Ewing's sarcoma and primitive neuroectodermal tumors

There has been an explosion of new knowledge regarding the Ewing family of tumors over the past 5 to 10 years. Classical Ewing's sarcoma and PNET are now known to be the same tumor with variable differentiation, defined by a translocation between the EWS gene on chromosome 22 with one of three ETS-like genes, especially the FLI-1 gene on chromosome 11. Molecular techniques used to identify this translocation along with the knowledge that the protein product of the MIC2 gene is highly expressed on the cell surface have greatly improved our diagnostic abilities in this family of tumors. Controversy still exists as to whether surgery improves event-free survival when compared with radiotherapy in Ewing's sarcoma. The high second tumor rate, if nothing else, has started moving many physicians to preferentially use surgery when the functional results are predicted to be reasonable. The addition of ifosfamide and etoposide to standard therapy in Ewing's sarcoma has improved survival for patients without metastases at presentation. However, outcome for patients with metastases or who develop metastases while on therapy or shortly thereafter remains poor. Preliminary reports of better outcome with megatherapy are interesting but not yet definitive. The decades ahead will probably see marked changes in therapy for Ewing's sarcoma. The unique translocation seen in virtually all of these tumors is a potential target for a "magic bullet" therapy, because the protein product of this translocation is present only in the malignant cells. Hopefully either immune modulation against this unique protein or further knowledge of how to use antisense genes will move us toward exquisitely targeted therapy in the Ewing family of tumors.