Revised text to state that genome-wide association studies have identified susceptibility loci for Ewing sarcoma at 1p36.22, 10q21, and 15q15. Deep sequencing through the 10q21.3 region identified a polymorphism in the EGR2 gene, which appears to cooperate with and magnify the enhanced activity of the gene product of the EWSR1-FLI1fusion that is seen in most patients with Ewing sarcoma. Also added text to state that three new susceptibility loci have been identified at 6p25.1, 20p11.22, and 20p11.23 (cited Machiela et al. as reference 17).
Revised Table 3 to include high-dose chemotherapy and autologous stem cell rescue as a standard treatment option for localized Ewing sarcoma.
Added text to state that for patients who undergo gross-total resection with microscopic residual disease, full-dose radiation therapy is indicated.
Added text about the results of the EURO-EWING-INTERGROUP-EE99 trial that investigated the role of high-dose therapy with busulfan-melphalan followed by stem cell rescue (cited Whelan et al. as reference 44).
Added text to state that one arm of the prospective, randomized EURO-EWING-INTERGROUP-EE99 trial demonstrated a benefit of high-dose therapy with busulfan-melphalan followed by stem cell rescue compared with continued chemotherapy for patients with localized tumor and poor response to initial chemotherapy (cited Whelan et al. as reference 18).
Added text to state that the role of high-dose therapy with busulfan-melphalan followed by stem cell rescue was investigated in the prospective, randomized EURO-EWING-INTERGROUP-EE99 trial. Among patients with isolated pulmonary metastases, there was no difference in 3-year event-free survival (cited Whelan et al. as reference 20).
Added Table 5 to summarize the results of studies that used cyclophosphamide and topotecan to treat patients with relapsed and/or refractory Ewing sarcoma (cited Farhat et al. and Kebudi et al. as references 14 and 15, respectively).
Added text to state that when combined, these studies accrued 99 patients and observed 3 complete remissions and 27 partial remissions. The objective response rate was 30%.
Added Table 6 to summarize the results of studies that used temozolomide and irinotecan to treat patients with relapsed and/or refractory Ewing sarcoma (cited Hernández-Marqués et al., McNall-Knapp et al., 2010 Wagner et al., 2013 Wagner et al., Bagatell et al., and Anderson et al. as references 16, 17, 18, 19, 20, and 22, respectively).
Added text to state that when combined, these studies accrued 176 patients and observed 18 complete remissions and 56 partial remissions. The objective response rate was 42%.
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