Bisogno G.,University of Padua |
Ferrari A.,Fondazione IRCCS Instituto Nazionale Tumori |
Bien E.,Medical University of Gdańsk |
Brecht I.B.,University Childrens Hospital Erlangen |
And 7 more authors.
Klinische Padiatrie | Year: 2012
The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs. © Georg Thieme Verlag KG Stuttgart New York.
Armeanu-Ebinger S.,University of Tübingen |
Bonin M.,University of Tübingen |
Habig K.,University of Tübingen |
Poremba C.,University Hospital |
And 6 more authors.
International Journal of Oncology | Year: 2011
Expression profiling of tumor tissue allows a systematic search for targeted therapies and offers relevant prognostic information. Molecular studies on rhabdomyosarcoma (RMS) revealed a more differentiated classification than the histological subgrouping into embryonal (RME) and alveolar (RMA) rhabdomyosarcoma, and reflected the chromosomal aberrations found in RMS. We addressed biological processes like cell migration and emerging drug resistance by expression profiling to identify mechanisms of metastasic invasion and differential response to chemotherapy in RMS. Gene expression analysis was performed in 19 RMS samples using the Affymetrix U133 Plus2 array. Validation of target genes was performed by qRT-PCR. Data were analyzed using Pathway analysis software. Involvement of these genes in invasion processes was evaluated in knock-down experiments using specific interference RNA and Matrigel™ invasion assay. In RMA tissues 211 of 534 genes were overexpressed, in RME tissues 323 genes were overexpressed. Pathway analysis software identified a group of genes involved in cell growth, morphology and motility. In patients with distant metastases especially transcription factors such as FOXF1 and LMO4 showed a high expression, which were described as determinants of tumor cell migration. Down-regulation of these factors inhibited the invasion of RMS cells >10-fold. Microarray technology is a powerful method not only to classify RMS samples, but also to identify major regulatory processes. Functional evaluation of LMO4 and FOXF1 identified targets of a molecular network for preventing metastatic invasion in RMS.
Pritchard-Jones K.,University College London |
Bergeron C.,Center Leon Berard |
De Camargo B.,Instituto Nacional Do Cancer |
Van Den Heuvel-Eibrink M.M.,Princess Maxima Center for Paediatric Oncology |
And 8 more authors.
The Lancet | Year: 2015
Background Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation. Methods For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m2 at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m2 given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants. Findings Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence. Interpretation Doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification. Funding See Acknowledgments for funders. © 2015 Pritchard-Jones et al. Open Access article distributed under the terms of CC BY.
Graf N.,Saarland University |
Van Tinteren H.,Netherlands Cancer Institute |
Bergeron C.,Institute dHemato Oncologie Pediatrique |
Pein F.,InstitutGustave Roussy |
And 7 more authors.
European Journal of Cancer | Year: 2012
Purpose: To determine the prognosis of children with stage II and III of low or intermediate risk histology (SIOP classification) in unilateral localised Wilms tumour (WT) after neoadjuvant chemotherapy according to the trial and study of the International Society of Paediatric Oncology, SIOP 93-01. Patients and methods: Patients with unilateral localised WT and stage II or III with low (LR) or intermediate risk (IR) histology between 6 months and 18 years of age, were selected from the total sample of patients registered in the SIOP 93-01 study between June 1993 and December 2001. All patients received 4 weeks of actinomycin-D/vincristine before surgery. Postoperative chemotherapy consisted of actinomycin-D, vincristine and epirubicin/doxorubicin for 27 weeks. Flank or whole abdomen irradiation was given for stage III. Event-free survival (EFS) and overall survival (OS) were analysed for various subgroups. Results: Of 1476 registered patients 594 (40%) met the inclusion criteria for this analysis. Four hundred and two (67%) had stage II disease and 563 (95%) had intermediate risk histology. Median tumour volume was 439 ml at diagnosis and 163 ml after preoperative chemotherapy. With a median follow-up of 8 years, 5-year EFS was 90% (95% confidence interval [95% CI]: 87-92%) and OS 95% (95% CI: 93-97%). Patients with stage III, blastemal type histology and a large volume at surgery had a worse outcome. Conclusion: Treatment for stage II and III LR or IR WT is successful in a neoadjuvant setting as advised by the SIOP. Stage, tumour volume and blastemal type histology are the most important prognostic factors. © 2012 Elsevier Ltd. All rights reserved.
Seitz G.,University Hospital of Tuebingen |
Dantonello T.M.,Olgahospital |
Int-Veen C.,Olgahospital |
Blumenstock G.,University of Tübingen |
And 7 more authors.
Pediatric Blood and Cancer | Year: 2011
+Background: To analyze the clinical course, treatment modalities, complications and outcome of patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma (BPRMS) treated on the CWS-96 trial. +Procedure: There were 85 patients with BPRMS enrolled and 63 patients with embryonal non-metastatic BPRMS were analyzed. Fifty-six patients received neoadjuvant chemotherapy and response was assessed radiographically after 9 weeks. Local therapy with radiation and or surgery was performed based on age, tumor size, and response. Patients were treated with adjuvant chemotherapy following local control. +Results: Patient's age ranged from 0 to 16 years with a median follow up of 5.3 years. Eighty nine percent of the patients had IRS group III disease. The 5-year overall survival (OS) for the whole group was 76.3±5.6% and the 5-year event-free survival (EFS) 69.8±6.2%. Seventeen patients underwent preoperative radiochemotherapy followed by tumor resection (5-year-OS: 87.8±8.1%). Eight patients were treated with solely radiochemotherapy (87.5±11.7%). Twenty-five patients received chemotherapy and tumor resection (OS: 83.6±7.5%). Thirteen patients underwent incomplete tumor resection and were treated with radiochemotherapy postoperatively (OS: 39.9±14.8%, P<0.05 vs. other groups). +Conclusions: Local therapy is an important factor for prognosis of localized embryonal BPRMS. Inadequate primary or secondary surgery compromises the outcome and should be avoided. Radiotherapy alone, complete surgical tumor resection or combined preoperative radiotherapy with surgical resection lead to similar good local control rates and prognosis. © 2010 Wiley-Liss, Inc..
Jaroch J.,Marciniak Hospital |
Kaminska-Kegel A.,Voivodeship Medical Center |
Brzezinska B.,Marciniak Hospital |
Kruszyneska E.,Marciniak Hospital |
And 4 more authors.
Polskie Archiwum Medycyny Wewnetrznej | Year: 2016
Introduction Evidence of left atrial appendage thrombogenic milieu (LAA TM) on transesophageal echocardiography (TEE) is recognized as a surrogate marker for an increased stroke risk. Although the CHA2DS2-VASc scale is commonly used as a measure of thromboembolic risk in patients with atrial fibrillation (AF), it was shown to have only low-to-moderate ability to predict the presence of LAA TM. The potential role of transthoracic echocardiography (TTE) in the refinement of clinical scales for the detection of LAA TM in patients with AF has been readdressed recently. Objectives The aim of the study was to identify the predictors of LAA TM among the components of the CHA2DS2-VASc scale and TTE parameters in patients scheduled for electrical cardioversion due to persistent AF. Patient s and methods We conducted a retrospective analysis of demographic, clinical, laboratory, echocardiographic, and medication data of 202 patients (123 men and 79 women; mean age, 65.6 years) with persistent AF, who underwent TEE before electrical cardioversion. Result s Duration of AF exceeding 1 year (odds ratio [OR] = 13.9; P = 0.02), left atrial diameter exceeding 51 mm (OR = 3.98; P = 0.009), left ventricular end-diastolic dimension (LVEDd) exceeding 52 mm (OR = 2.42; P = 0.01), and radiographic evidence of aortic plaques (OR = 2.97; P = 0.007) were shown to be independent predictors of LAA TM in a multivariate regression analysis. Conclusions The CHA2DS2-VASc scale did not predict the presence of LAA TM on TEE in patients scheduled for electrical cardioversion due to persistent AF. Of the CHA2DS2 -VASc components, only radiographic evidence of aortic plaques, and of TTE parameters, only left atrial enlargement and LVEDd were independent predictors of LAA TM. A comprehensive clinical and echocardiographic assessment of individual risk is indicated in patients before electrical cardioversion due to persistent AF. © Medycyna Praktyczna, Kraków 2016.
PubMed | University of Padua, University Childrens Hospital, Municipal Hospital Dortmund, Gustave Roussy Cancer Campus and 8 more.
Type: | Journal: Pediatric blood & cancer | Year: 2016
The aim of this retrospective international analysis was to evaluate the role of risk factors in pediatric patients with adrenocortical carcinoma (ACC) observed in European countries (2000-2013) in an attempt to identify factors associated with poor prognosis.Data were retrieved from databases of Germany, France, Poland, and Italy, which form the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). Patients were less than 18 years old, with at least one of the following tumor-related risk factors: metastases, volume more than 200 cmEighty-two patients were evaluated: 62 with localized disease and 20 with metastases. The 3-year progression-free survival (PFS) and overall survival (OS) were 39% and 55% for the whole population, respectively, and 51% and 73% for localized diseases, respectively. Concerning the whole population, PFS and OS were influenced by distant metastases, tumor volume, lymph node involvement, age, and presence of two or more risk factors. Factors significant only at OS were vascular involvement and incomplete surgery. At multivariable analysis, the main factors at PFS were volume more than 200 cmDistant metastases and large tumor volume were the main unfavorable prognostic factors. Presence of two or more factors related to ACC was associated with an aggressive behavior of disease.
Bien E.,Medical University of Gdańsk |
Rapala M.,Marciniak Hospital |
Krawczyk M.,Medical University of Gdańsk |
Balcerska A.,Medical University of Gdańsk
Journal of Cancer Research and Clinical Oncology | Year: 2010
Purpose The objective of this study is to establish the clinical utility of serum soluble IL-2 receptor (sIL-2Rα) and B2-Microglobulin (B2-M) as markers for diagnosis, prognosis and treatment monitoring in childhood soft tissue sarcomas (STS). Methods sIL-2Rα and B2-M were measured prospectively before treatment, in complete remission (CR) during and after therapy and at relapse by ELISA in 35 children with STS and in 50 healthy controls (once). Results The sIL-2Rα correlated with age thus it was presented as multiplication of the upper normal range for age. Pre-treatment level of sIL-2Rα but not of B2-M exceeded significantly that of healthy children. SIL-2Rα levels were significantly increased in patients with advanced stages, poor-risk histology and non-responders. Patients' age >10 years, unfavourable tumour localisation and incomplete resection were not accompanied by the increase of any marker. Good response to chemotherapy was paralleled by a decline of sIL-2Rα pre-treatment level (P < 0.001). None of the markers predicted event-free and overall survival. At relapse, sIL-2Rα increased; however; it was not statistically different from the level stated in remission. Monitoring of B2-M during therapy did not reXect the disease course. After completion of therapy the levels of sIL-2Rα and B2- M were significantly lower than during treatment, but still higher than in controls. Conclusions sIL-2Rα was proven to be a promising marker for diagnosis and treatment monitoring in children with STS. It correlated also with some clinical variables known to have important prognostic role (STS stage, histological subtype and response to therapy); however, it failed to predict EFS and OS. To the contrary, B2-M proved to have no clinical value in the diagnostics, prognostics and treatment monitoring in paediatric STS. © Springer-Verlag 2009.
Bien E.,Medical University of Gdańsk |
Balcerska A.,Medical University of Gdańsk |
Niedzwiecki M.,Medical University of Gdańsk |
Krawczyk M.,Medical University of Gdańsk |
And 3 more authors.
Cytokine | Year: 2011
Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a "false" one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers' elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between "real" relapse and "false" sIL-2Rα increase due to G-CSF administration or CVC-related sepsis. © 2011 Elsevier Ltd.
Godzinski J.,Marciniak Hospital |
Godzinski J.,Wroclaw Medical University
Journal of Indian Association of Pediatric Surgeons | Year: 2014
This paper attempts to briefly describe the International Society of Paediatric Oncology (SIOP) policy of treatment of nephroblastoma since first study (SIOP 1) launched in 1971 until today. It focuses on the advantages of the preoperative chemotherapy and the stratification of patients induced this way. Marked efficacy of the pretreatment opened the way for less aggressive surgical management also in case of the "so-called" regular unilateral cases: Nephron-sparing surgery and minimal invasive techniques will probably find its place in this field of pediatric surgical oncology; however, very careful selection of cases must be the priority.