Clinical significance of Vascular Endothelial Growth Factor-A expression in Ewing's sarcoma.

The aim of our study was to gain further insight into the role of angiogenesis in Ewing's sarcoma. To this end, expression of Vascular Endothelial Growth Factor-A (VEGF-A), its receptors VEGFR-1 and -2 and microvessel density (MVD) were evaluated by quantitative immunohistochemistry in pretherapeutic biopsies of 40 patients with Ewing's sarcoma treated within standardised neoadjuvant protocols. Median expression levels were 1.5 arbitrary units (AU) for VEGF-A, 8.2 AU for VEGFR-2 and median MVD was 96/0.26 mm(2). VEGFR-1 was expressed in 12.5% of the samples, only. Ten-year relapse free and overall survival rates were significantly higher for patients with high VEGF-A expression (60% versus 29%, p=0.0216 and 65% versus 25%, p=0.013, respectively). Multivariate Cox regression analysis revealed that VEGF-A expression was an independent prognostic factor for survival. In conclusion, these data suggest that the angiogenic mediator VEGF plays an important prognostic role in Ewing's sarcoma.

Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors.

BACKGROUND: The prognosis of Ewing tumor (ET) patients has significantly improved to cure rates approximating 70%. The prognosis in relapse, however, is poor. Promising response rates have recently been reported for the combination of topotecan (TOPO) and cyclophosphamide (CYC) encouraging wider application of this combination in patients with relapsed ETs. This report summarizes the experience of patients treated with TOPO/CYC for recurrent or refractory disease within the German ET trials. PROCEDURE: Fifty-four patients aged 3.2-49.5 (median: 17.4) years received TOPO (0.75 mg/m2/day, days 1-5) and CYC (250 mg/m2/day, days 1-5) following first (40) or second (6) relapse or progression under first-line therapy (8). RESULTS: A median of 3 (range: 1-11) TOPO/CYC courses were given. Sixteen patients (32.6%) showed partial response (PR), 13/49 (26.5%) had stable disease (SD), 14/49 (28.6%) progressed, 2/49 (4.1%) showed a mixed response (MR). In 4 patients response was not documented, 5/54 patients with complete initial resection at the diagnosis of relapse were excluded from the response analysis. At completion of relapse therapy, 24/54 patients had entered complete (19) or partial (5) remission, 2 had SD, 26 showed progression, information was unavailable in 2 patients. Of the 19 relapse patients achieving complete response (CR), 10 maintained remission (52.6%). At the time of evaluation, after a median follow-up for survivors of 23.1 (range: 7.8-59.8) months from the event prompting TOPO/CYC treatment, 14/54 patients (25.9%) were in continuous complete (13) or partial (1) remission. Overall survival (OAS) after 1 year was 0.61 (95%-CI 0.47-0.74). CONCLUSION: TOPO/CYC is active in relapsed ETs and warrants further evaluation.