Treatment for soft tissue sarcoma in childhood and adolescence. Austrian results within the CWS 96 study.
ABSTRACT The aim of the CWS 96 Study was to achieve an optimal treatment in children and adolescents with soft tissue sarcoma (STS) implementing a further refinement of risk-adapted allocation to chemotherapy, surgery and radiotherapy.
Treatment stratification was based on tumour histology, TNM status, postsurgical stage, localisation and age. Local tumour control was ensured by surgery and risk-adapted radiotherapy.
From 1995 to 2002, 89 patients were registered in Austria. The 3-year event-free survival (EFS) and overall survival rates (OS) were 63% +/- 6% and 71% +/- 6%, respectively. 59/89 patients had localised RMS-like (rhabdomayosarcoma) STS (EFS 73% +/- 7%), 14 had localised NON-RMS STS (EFS 54% +/- 16%) and 15 patients had metastatic disease at diagnosis (EFS 33% +/- 12%), 1 patient had fibromatosis. The EFS rates at 3 years in patients with localised RMS-like tumours according to risk group were 92% +/- 8% for low and standard risk (12 patients) and 67% +/- 8% for high risk (47 patients). Favourable primary tumour sites of nonmetastatic RMS-like STS i.e. orbit, head/neck nonparameningeal or genitourinary non-bladder/prostate were diagnosed in 15 patients (1/15 patients died). In 44 patients with unfavourable localisation such as parameningeal, genitourinary bladder/prostate, extremity and others, 7 deceased. The 3 year EFS according to histology in patients with RMS-like STS was 61% +/- 11% for RME (embryonal RMS ) (28 patients) and 71% +/- 15% for RMA (alveolar RMS) (10 patients). The most common treatment failure was local relapse occurring in 21% of patients in the high-risk group.
Risk-adapted individualisation of treatment led to a reduction of chemotherapy in the low and standard risk group without compromising survival. The outcome of RME and RMA was similar in this cohort of patients. These preliminary results after a median observation time of 2.5 years confirm the CWS 96 strategy.
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ABSTRACT: BACKGROUND: Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. METHODS: Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. RESULTS: Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 ± 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection + radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 ± 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. CONCLUSION: Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.Pediatric Blood & Cancer 02/2013; · 2.35 Impact Factor
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ABSTRACT: Optimal management of rhabdomyosarcoma requires establishing the correct pathologic diagnosis, histologic sub-type, primary site, extent of disease (Stage), and extent of resection (Group). Based on these features, cooperative groups in North America and Europe have defined risk-adapted treatments that include surgery, chemotherapy, and usually radiotherapy. This article focuses on recent findings that can impact or have already impacted rhabdomyosarcoma treatment guidelines and highlights controversies that should be addressed in order to improve outcome for children with rhabdomyosarcoma. Rhabdomyosarcoma is currently sub-classified in children based on histology into the favorable embryonal/botryoid/spindle cell types and the unfavorable alveolar form. Risk group assignment depends in part on histologic sub-type. Alveolar rhabdomyosarcoma is sometimes associated with chromosomal translocations, which impact clinical behavior. An important ongoing debate is whether molecular diagnostic tools to identify chromosomal translocations and/or define gene expression profiles should be used to sub-classify rhabdomyosarcoma rather than histology. Clinical trials continue to evaluate retrospective as well as prospective cohorts in order to carefully determine the impact of histology versus biologic features on outcome in the context of specific therapeutic regimens. Most rhabdomyosarcoma recurrences involve the primary site or adjacent region. Cooperative groups continue to investigate new approaches to local control in order to reduce local recurrences and sequelae associated with local therapy. Delaying primary resection until after chemotherapy has started appears to increase the number of tumors that can be completely resected with acceptable morbidity in some primary sites. Radiation dose reductions following delayed primary resection have been investigated. Although outcomes appear similar to the conventional approach of full-dose radiotherapy without delayed primary resection, long-term effects of the two approaches have not been rigorously compared. Early evidence suggests that newer methods of delivering radiotherapy, including intensity-modulated radiotherapy (IMRT), proton beam radiotherapy, and brachytherapy maintain efficacy but may reduce long-term sequelae compared with 3-dimensional conformal radiotherapy. Chemotherapy regimens defined by the cooperative groups vary by risk group. The most commonly used regimens include vincristine and dactinomycin in combination with an alkylating agent, either cyclophosphamide or ifosfamide. In order to improve outcomes, recent clinical trials have introduced new chemotherapeutic agents (e.g. topotecan, carboplatin, or epirubicin) into the treatment regimens. However, outcomes have not been significantly impacted. Novel chemotherapy administration schedules have been tested in patients with metastatic rhabdomyosarcoma, including interval compressed dosing or maintenance therapy, and may be promising. Molecularly targeted agents are currently under investigation in combination with chemotherapy for patients with recurrent or metastatic rhabdomyosarcoma. It is hoped that these novel agents will benefit all patients with rhabdomyosarcoma in the future.Paediatric Drugs 12/2012; 14(6):389-400. · 1.72 Impact Factor
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ABSTRACT: Purpose Children suffering from paratesticular rhabdomyosarcoma (RMS) have a favorable prognosis. Surgical treatment problems are inadequate primary transscrotal approaches, incomplete tumor resections, and the necessity of secondary hemiscrotectomy. The aim of this study was to evaluate the necessity of hemiscrotectomy regarding local relapse and outcome. Materials and Methods One-hundred-seventy-three patients with diagnosis of paratesticular RMS were enrolled into the trials between 1986 and 2008. Seventeen patients were excluded due to an incomplete data set and alveolar histology. One-hundred-fifty six patients with embryonal subtype (RME) were finally analyzed. All patients were treated according to the treatment protocols of the Cooperative Soft Tissue Sarcoma (CWS) trials including multiagent chemotherapy, tumor resection and / or radiotherapy. Results The five year overall survival rate was 91.5% ± 2.4 for all RME patients. Twenty-eight patients underwent transscrotal approaches initially. 12/28 RME patients were treated with hemiscrotectomy (5-year-EFS 91.7%±8) and 16/28 patients without hemiscrotectomy (5-year-EFS 93.8%±6.1). Additionally, 13/156 patients underwent an inguinal approach and hemiscrotectomy due to suspicious tumor infiltration of the scrotal skin (5-year-EFS was 84.6%±10). Relapses were observed in 3/12 patients after transscrotal approach and hemiscrotectomy (one locoregional lymph node and two metastatic). One metastatic relapse was observed in the patients treated with a transscrotal approach without hemiscrotectomy. 1/13 patients with inguinal approach and hemiscrotectomy had locoregional relapse and died of disease. Conclusions Hemiscrotectomy seems not to be mandatory in patients after transscrotal approaches regarding outcome and local relapse. Nevertheless, hemiscrotectomy should be probably performed if the scrotal skin is infiltrated.The Journal of urology 01/2014; · 3.75 Impact Factor