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Pizer B.,Oncology Unit | Donachie P.H.J.,Childrens Cancer and Leukaemia Group | Robinson K.,Childrens Cancer and Leukaemia Group | Taylor R.E.,University of Swansea | And 4 more authors.
European Journal of Cancer

Background: The treatment of previously irradiated patients with recurrent central nervous system primitive neuroectodermal tumours (PNETs) is a considerable challenge. A study was undertaken to attempt to improve the outcome for such patients using a high dose chemotherapy (HDCT) based strategy. Methods: Between 2000 and 2007, 40 patients with relapsed medulloblastoma (MB) and 5 with relapsed supratentorial PNETs (StPNETs) were accrued. All but one had received prior craniospinal radiotherapy. Patients were initially treated with cyclophosphamide (4 g/m 2) together with surgery or local radiotherapy where appropriate. If complete or near complete remission was achieved, the patient proceeded to receive two sequential courses of HDCT with stem cell rescue. The first course consisted of thiotepa (900 mg/m 2) and the second carboplatin (AUC 21). Results: All five patients with StPNET died of tumour progression with a median OS of 0.4 years. Nineteen of the 40 patients with relapsed MB underwent surgery. Radiotherapy was administered to eight patients. All patients received at least one course of cyclophosphamide. Only 22 MB patients progressed to the HDCT phase; 10 patients received thiotepa only and 12 thiotepa and carboplatin. At a median follow-up of 7.4 years (Range 2.8-8.2 years), only three MB patients are still alive, one following a further relapse. Three and 5 year OS was 22.0% and 8.2%, respectively and 3 and 5 year EFS was 14.6% and 8.7%, respectively. Conclusion: This national study based on a strategy including a particular tandem HDCT regimen showed no benefit for previously irradiated patients with relapsed StPNET and very limited benefit for patients with relapsed medulloblastoma. © 2011 Elsevier Ltd. All rights reserved. Source

Gaspar N.,CNRS Gustave Roussy Institute | Gaspar N.,Societe Francaise de Lutte Contre les Cancers et les Leucemies de LEnfant et de LAdolescent | Hawkins D.S.,Seattle Childrens Hospital | Hawkins D.S.,Childrens Oncology Group | And 43 more authors.
Journal of Clinical Oncology

Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed. © 2015 by American Society of Clinical Oncology. Source

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