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Martin Stahl,
Andreas Ranft, Michael Paulussen,
Tobias Bölling,
Volker Vieth,
Stefan Bielack,
Irene Görtitz,
Gabriele Braun-Munzinger,
Jendrik Hardes,
Heribert Jürgens,
Uta Dirksen
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ABSTRACT: The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.
We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow-up or death.
Median follow-up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2-24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five-year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5-year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five-year OSr was 0.07 (SE = 0.01) in patients who relapsed 0-2 years after the diagnosis of primary disease, as compared to a 5-year OSr of 0.29 (SE = 0.03) when relapse occurred later.
5-year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse.
Pediatric Blood & Cancer 03/2011; 57(4):549-53. · 1.89 Impact Factor
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Ruth Ladenstein,
Ulrike Pötschger,
Marie Cécile Le Deley,
Jeremy Whelan, Michael Paulussen,
Odile Oberlin,
Henk van den Berg,
Uta Dirksen,
Lars Hjorth,
Jean Michon,
Ian Lewis,
Alan Craft,
Heribert Jürgens
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ABSTRACT: To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept.
From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT).
After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score <or= 3 (82 patients), 25% for score more than 3 to less than 5 (102 patients), and 10% for score >or= 5 (70 patients; P < .0001).
PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.
Journal of Clinical Oncology 07/2010; 28(20):3284-91. · 18.37 Impact Factor
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Michael Paulussen,
Alan W Craft,
Ian Lewis,
Allan Hackshaw,
Carolyn Douglas,
Jürgen Dunst,
Andreas Schuck,
Winfried Winkelmann,
Gabriele Köhler,
Christopher Poremba,
Andreas Zoubek,
Ruth Ladenstein,
Henk van den Berg,
Andrea Hunold,
Anna Cassoni,
David Spooner,
Robert Grimer,
Jeremy Whelan,
Anne McTiernan,
Herbert Jürgens
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ABSTRACT: The European Intergroup Cooperative Ewing's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk (SR) patients and whether the addition of etoposide improves survival in high-risk (HR) patients.
SR patients (localized tumors, volume <100 mL) were randomly assigned to receive four courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume >or=100 mL or metastases) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival (EFS; defined as the time to first recurrence, progression, second malignancy, or death) and overall survival (OS).
A total of 647 patients were randomly assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA. The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to 2.03), respectively. There was a higher incidence of hematologic toxicities in the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA) indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12) and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed greater among patients without metastases (hazard ratio = 0.79; P = .16) than among those with metastases (hazard ratio = 0.96; P = .84).
Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.
Journal of Clinical Oncology 10/2008; 26(27):4385-93. · 18.37 Impact Factor
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ABSTRACT: In the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92, whole lung irradiation (WLI) was performed in patients with primary lung metastases. This retrospective analysis evaluates the pulmonary function and the outcome of patients with exclusively pulmonary metastases.
Between 1990 and 1999, 99 patients were registered into the EICESS-92-study trial with exclusively pulmonary metastases of Ewing tumors. The multimodal treatment regimen included polychemotherapy and local therapy to the primary tumor. WLI was performed with a dose between 12-21 Gy. 70 patients were treated with WLI, 13 of them received a further boost to their primary tumor in the thorax up to a cumulative dose of 54 Gy.
Pulmonary function tests were available for 37 patients treated with WLI (+/- boost). None, mild, moderate or severe pulmonary complications were seen in 43%, 29%, 21% and 7% of patients treated with WLI without further boost (median follow-up 25.2 months). Patients with an additional radiation boost or surgery to the thorax showed slightly higher rates of complications. Overall survival (OAS) showed a trend towards better results for patients with WLI (5-year-OAS: 0.61 for WLI vs. 0.49 for no WLI, p = 0.36).
These data indicate a benefit and acceptable toxicity for WLI in the presented collective of patients. As long as there is no randomized prospective analysis, the present data confirm the indication for WLI in Ewing tumor patients with primary exclusively lung metastases.
Strahlentherapie und Onkologie 05/2008; 184(4):193-7. · 3.56 Impact Factor
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ABSTRACT: OPINION STATEMENT: Bone tumors, particularly osteosarcomas and members of the Ewing Sarcoma Family of Tumors (ESFT), are typical malignancies of adolescents and young adults. Current diagnostic and therapeutic guidelines for patients of all ages were developed in this specific age group. The aim of bone sarcoma therapy should be to cure the patient from both the primary tumor and all (micro-)metastatic deposits while maintaining as much (extremity) function and causing as few treatment-specific late effects as possible. Bone sarcoma therapy requires close multidisciplinary cooperation. Usually, it consists of induction chemotherapy, followed by local therapy of the primary tumor (and, if present, primary metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma should be surgery whenever feasible. Surgery is also gaining importance in ESFT, which was long considered a domain of radiotherapy. Modern reconstructive techniques continue to expand the indications for limb salvage, particularly for patients who have not yet reached skeletal maturity. Treatment within the framework of prospective, multi-institutional trials should be considered standard of care not only for children, but also for affected adolescents and (young) adults. Such trials are essential in guaranteeing that all patients have access to appropriate care and that progress from biological studies can be translated into prognostic improvements without undue delay. The rarity of bone sarcomas increasingly requires trials to be multinational.
Current Treatment Options in Oncology 03/2008; 9(1):67-80. · 2.68 Impact Factor
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ABSTRACT: Ewing's tumors (ET) are rare in patients over the age of 40 years. Published data on presentation, treatment, and clinical outcome are limited.
We present a retrospective analysis of data from 47 patients in this age group diagnosed with ET and enrolled in the 2 consecutive trials, EICESS 92 and EURO-E.W.I.N.G. 99. The median age at diagnosis was 47.7 years (range, 40-68.6 years).
The median follow-up was 2.23 years from diagnosis (range, 0.35-12.92 years). 72.3% of patients were found to have localized disease, and 27.7% had primary metastases. Good clinical response to induction therapy was observed in 55%, and 73% of patients showed good histological response. The event-free survival was 0.77 at 1 year and 0.50 at 3 years (n = 44).
ET are rare in patients over the age of 40 years. With adequate multimodal therapy, the results in terms of survival are comparable to those in adolescence. Specific age-adapted treatment regimens are not established. Patients should be enrolled in international trials, and if necessary treatment should be adjusted for lower tolerance and co-morbidity.
Onkologie 02/2008; 31(12):657-63. · 0.87 Impact Factor
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ABSTRACT: Background:In the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92, whole lung irradiation (WLI) was performed in patients
with primary lung metastases. This retrospective analysis evaluates the pulmonary function and the outcome of patients with
exclusively pulmonary metastases.
Patients and Methods:Between 1990 and 1999, 99 patients were registered into the EICESS-92-study trial with exclusively pulmonary metastases of
Ewing tumors. The multimodal treatment regimen included polychemotherapy and local therapy to the primary tumor. WLI was performed
with a dose between 12–21 Gy. 70 patients were treated with WLI, 13 of them received a further boost to their primary tumor
in the thorax up to a cumulative dose of 54 Gy.
Results:Pulmonary function tests were available for 37 patients treated with WLI (± boost). None, mild, moderate or severe pulmonary
complications were seen in 43%, 29%, 21% and 7% of patients treated with WLI without further boost (median follow-up 25.2
months). Patients with an additional radiation boost or surgery to the thorax showed slightly higher rates of complications.
Overall survival (OAS) showed a trend towards better results for patients with WLI (5-year-OAS: 0.61 for WLI vs. 0.49 for
no WLI, p = 0.36).
Conclusion:These data indicate a benefit and acceptable toxicity for WLI in the presented collective of patients. As long as there is
no randomized prospective analysis, the present data confirm the indication for WLI in Ewing tumor patients with primary exclusively
lung metastases.
Hintergrund:In der European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 wurde bei Patienten mit primären Lungenmetastasen
eine Ganzlungenbestrahlung durchgeführt. Für diese retrospektive Analyse wurden Lungenfunktion und Behandlungsergebnisse von
Patienten mit ausschließlich pulmonaler Metastasierung analysiert.
Patienten und Methodik:Von 1990 bis 1999 wurden 99 Patienten mit primären Lungenmetastasen ohne weitere Metastasierung von Ewing-Tumoren in der EICESS-92-Studie
registriert. Das multimodale Therapieregime beinhaltete Polychemotherapie und Lokaltherapie für den Primarius. Die Ganzlungenbestrahlung
wurde mit Dosen von 12 bis 21 Gy durchgeführt. 70 Patienten erhielten eine Ganzlungenbestrahlung, 13 davon mit einem weiteren
Boost auf den Primarius im Thorax bis maximal kumulativ 54 Gy.
Ergebnisse:Lungenfunktionsanalysen waren bei 37 Patienten mit Ganzlungenbestrahlung (± Boost) zu erheben. Keine, milde, moderate oder
schwere pulmonale Einschränkungen waren in 43%, 29%, 21% und 7% der Patienten mit alleiniger Ganzlungenbestrahlung zu erheben
(mediane Nachbeobachtungszeit 25,2 Monate) (Tabellen 2 und 3: Vergleich der Patientencharakteristika von Patienten mit/ohne
Funktionseinschränkungen (Tabelle 2) bzw. mit/ohne Lungenfunktionsprüfung im Verlauf (Tabelle 3). Patienten mit einem zusätzlichen
Boost oder einer Operation am Thorax (Tabelle 1) zeigten etwas höhere Komplikationsraten. Im Trend zeigte das Gesamtüberleben
für die Patienten, die eine Ganzlungenbestrahlung erhalten hatten, bessere Ergebnisse (Abbildung 1: Gesamtüberleben bei Patienten
mit und ohne Ganzlungenbestrahlung; 5-Jahres-Gesamtüberleben: 0,61 für Ganzlungenbestrahlung vs. 0,49 für Nicht-Ganzlungenbestrahlung,
p = 0,36).
Schlussfolgerung:Diese Daten weisen auf einen Vorteil und eine akzeptable Toxizität bei Ganzlungenbestrahlung im präsentierten Kollektiv hin.
Solange keine Ergebnisse von prospektiven randomisierten Studien vorliegen, unterstützen die hier gezeigten Daten die Indikation
zur Ganzlungenbestrahlung bei Patienten mit solitären primären Lungenmetastasen eines Ewing-Tumors.
Strahlentherapie und Onkologie 01/2008; 184(4):193-197. · 3.56 Impact Factor
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ABSTRACT: 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.
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).
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).
TOPO/CYC is active in relapsed ETs and warrants further evaluation.
Pediatric Blood & Cancer 12/2006; 47(6):795-800. · 1.89 Impact Factor
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ABSTRACT: The therapeutic benefit and side-effect profile of gemcitabine in adults with relapsed solid tumors is well known. So far, few data are available about its significance in pediatric relapsed solid tumors. To determine the efficacy and tolerability of gemcitabine in children, the drug was administered by intravenous short-term infusion over 30 min at a dose of 1200 mg/m2 weekly for 3 weeks as one cycle in children with relapsed solid tumor of embryonic or mesenchymal origin. From May 2003 to September 2004, 14 male and six female patients (2-23, median 15.8 years) were recruited for this prospective open-label phase II study (two-step Simon design). The patients suffered from rhabdomyosarcoma (n=8), Ewing's sarcoma (n=4), osteosarcoma (n=2), neuroblastoma (n=3), hepatoblastoma (n=2) and nephroblastoma (n=1). Median duration of therapy was 27.5 days (7-99), corresponding to 4.0 (2-11) infusions of gemcitabine. Two patients (neuroblastoma and Ewing) had stable disease documented for 69 and 70 days, whereas no objective responses were observed. In 34/94 administered infusions; doses had to be reduced or omitted for grade 3-4 hematotoxicity. Minimal activity was observed in this cohort of children with a wide spectrum of mesenchymal and embryonic tumors. Given the relatively low dose of gemcitabine administered, this study does not exclude the possibility of activity at higher doses. Secondly, the tolerability of gemcitabine in children was consistent with that expected in adults. For further studies in this population, we recommend the use of gemcitabine in combination with other agents.
Anti-Cancer Drugs 09/2006; 17(7):859-64. · 2.41 Impact Factor
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ABSTRACT: 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.
European Journal of Cancer 09/2006; 42(12):1904-11. · 5.54 Impact Factor
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Christine Juergens MD,
Claire Weston MSc,
Ian Lewis MD,
Jeremy Whelan MD,
Michael Paulussen MD,
Odile Oberlin MD,
Jean Michon MD,
Andreas Zoubek MD,
Herbert Juergens MD,
Alan Craft MD,
Christine Juergens,
Claire Weston,
Ian Lewis,
Jeremy Whelan, Michael Paulussen,
Odile Oberlin,
Jean Michon,
Andreas Zoubek,
Herbert Juergens,
Alan Craft
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ABSTRACT: Background
The EUROpean Ewing tumour Working Initiative of National Groups 1999 (EURO-E.W.I.N.G. 99) protocol prescribes six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) as intensive induction chemotherapy for Ewing tumors (ET). Granulocyte-colony stimulating factor (G-CSF) is recommended. Adverse reactions (AR) were evaluated; quality assurance of data collection reviewed.ProcedureSafety data from 4,746 courses of VIDE in 851 patients less than 50 years with ET were collected using a checklist and evaluated using descriptive statistics with sub-groups including gender, age, and tumor volume, analyzed by Wilcoxon and Kruskal–Wallis tests.ResultsMyelosuppression and infections were the major AR but with appropriate supportive therapy targeted dose intensity was maintained. Five VIDE-related deaths with three due to sepsis were reported. Renal and cardiac toxicity were reflected by glomerular filtration rate (GFR) <39 ml/min/1.73m2 in 0.1%, tubular phosphate reabsorption ≤0.80 in 1.9%, and left ventricular shortening fracture <28% in 2.5% VIDE courses. Statistically significant gender-associated AR concerning hemoglobin and platelets were observed with females > males as were age-associated AR concerning hemoglobin, WBC, platelets, stomatitis, and vomiting with AR decreasing with age, that is, children > adolescents > adults. No association of AR to tumor volume was found. In VIDE courses with and without G-CSF, neutropenia-related fever in 60.8% and 65.8%, and infection in 54.7% and 61.0% courses, respectively, were recorded.ConclusionsAR under VIDE remained within the expected range. Some AR, for example, hematotoxicity were significantly influenced by age and gender but not by tumor volume. G-CSF did not significantly influence neutropenia-related fever and infection. Solicited safety collection with checklists adequately reflects the burden per course. Pediatr Blood Cancer © 2006 Wiley-Liss, Inc.
Pediatric Blood & Cancer 06/2006; 47(1):22 - 29. · 1.89 Impact Factor
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ABSTRACT: Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control-either surgery, radiation or a combination-and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.
The Oncologist 06/2006; 11(5):503-19. · 3.91 Impact Factor
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Andreas Schuck,
Susanne Ahrens,
Ines von Schorlemer,
Michaela Kuhlen, Michael Paulussen,
Andrea Hunold,
Georg Gosheger,
Winfried Winkelmann,
Jürgen Dunst,
Normann Willich,
Heribert Jürgens
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ABSTRACT: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors.
A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence.
A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found.
Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.
International Journal of Radiation OncologyBiologyPhysics 01/2006; 63(5):1562-7. · 4.11 Impact Factor
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ABSTRACT: Ein 14 Jahre alter Junge klagt seit einigen Wochen über Schmerzen im rechten Oberschenkel, die bei Belastung zunehmen, aber
auch nachts fortbestehen. In jüngster Zeit ist eine Schwellung in dem betroffenen Bezirk hinzugetreten. Röntgenbild, Kernspintomographie
und Knochenszinti graphie sind verdächtig für das Vorliegen eines bös artigen Knochentumors. Der Patient wird in einem pädiatrisch-onkologischen
Zentrum vorgestellt. Histologisch wird ein Ewing-Sarkom nachgewiesen. Der Patient erhält eine sys temische Chemotherapie,
das betroffene Knochenareal wird operativ entfernt und endoprothetisch überbrückt, das Kom partiment nachbestrahlt. Fünf Jahre
später ist der Junge in anhaltender Erstremission seiner Tumorerkrankung.
Ewing-Sarkome sind die zweithäufigsten primären Knochentumoren im Kindes- und Jugendalter. Mit multimo da ler Therapie liegen
die Heilungsraten bei über 50%. Vordring lich ist eine rechtzeitige Diagnose: Fortbestehende Knochenschmerzen bei Kindern
und Jugendlichen müssen innerhalb von 4 Wochen differenzialdiagnostisch abgeklärt sein.
12/2005: pages 894-910;
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ABSTRACT: Malignancies from the Ewing family of tumors and acute lymphoblastic leukemia (ALL) are not known to be associated with each other. A 5-year-old girl was incidentally found to suffer from acute lymphoblastic leukemia during bone marrow staging for Ewing sarcoma of the radius. The simultaneous presence of two distinct neoplasms was confirmed by RT-PCR, with EWS/FLI1 type 1 rearrangement in the bone tumor and TEL/AML1 rearrangement in the marrow. She was treated with chemotherapy, radiotherapy, and surgery and was in remission of both diseases 31 months after diagnosis.
Pediatric Blood & Cancer 12/2005; 45(6):846-9. · 1.89 Impact Factor
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Andreas Schuck,
Victoria Hamelmann,
Jürgen H Brämswig,
Stefan Könemann,
Claudia Rübe,
Stefan Hesselmann,
Dorothea Riesenbeck,
Ekkehard Horst,
Tobias Bölling, Michael Paulussen,
Heribert Jürgens,
Normann Willich
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ABSTRACT: To analyze the effect of pelvic radiotherapy on ovarian function in prepubertal and pubertal girls and young adult women.
In a retrospective monoinstitutional analysis, patients < 30 years of age at diagnosis were included who had been irradiated between 1979 and 1998. The main tumor types were Hodgkin's disease (38%), Ewing's sarcoma (20%) and nephroblastoma (11%). Patients were classified into three groups according to the position of the ovary in relation to the radiation portals. Group 1 was defined by direct irradiation of both ovaries. Group 2 patients were included with both ovaries potentially located in the radiation portals. In group 3, at least one ovary was not directly irradiated. The median follow-up was 128 months.
16 of 55 analyzed patients were categorized in group 1. In ten of these patients, hormone status was evaluable. The ovarian doses were >/= 15 Gy. Except for one patient treated with 15 Gy all developed hormone failure. Eight of 14 patients of group 2 were evaluable. Seven of these patients developed ovarian failure. 19 of 24 patients in group 3 were evaluable. Nine of these patients developed ovarian failure. The observed difference in the rate of ovarian failure between the groups is statistically significant (p = 0.045).
All patients receiving > 15 Gy to the ovaries developed hormone failure. In one case of a patient receiving an ovarian dose of 15 Gy, hormone failure was not found. In case of pelvic irradiation excluding at least one ovary, approximately half of the patients developed ovarian dysfunction, probably also due to the effects of polychemotherapy.
Strahlentherapie und Onkologie 08/2005; 181(8):534-9. · 3.56 Impact Factor
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ABSTRACT: In 1998, a prospective multicenter pilot study of the 'Late Effects Surveillance System' (LESS) was started to investigate late effects of patients with Ewing, osteo- or soft-tissue sarcoma.
Two hundred thirty patients were included in this pilot study. The patients were treated between 1/1/1998 and 6/30/1999 according to the sarcoma protocols COSS-96, CWS-96, and EICESS-92, the median cumulative doses of the focussed drugs were for cisplatin: 360 mg/m(2), for doxorubicin: 270 mg/m(2), and for ifosfamide: 24 g/m(2). The patients were investigated using an organ related standardized screening methodology. We report on toxicities in the first year after cessation of therapy-the beginning of the patient follow-up-and the feasibility of LESS.
Cardiotoxicity: 16/129 (12%) patients treated with doxorubicin exhibited a reduced systolic heart function (fractional shortening (FS) <29%). Altogether three patients required cardiac drug therapy. Ototoxicity: In 5/73 (7%) patients treated with cisplatin a hearing deficit <4 kHz (>20 dB) was found. One patient needed a hearing aid. Nephrotoxicity: 2 of 214 (1%) patients treated with ifosfamide suffered from a tubulopathy, which required supplementation therapy. 10/50 (20%) showed a reduced fractional phosphate reabsorption. Incidence of hypomagnesemia was significantly increased in patients additionally treated with cisplatin.
Some relevant impairments are noted in the first year after antineoplastic therapy. We expect to detect more major late sequelae in our prospective study during the increasing posttherapeutic interval. Our pilot study shows the feasibility of the methodology.
Pediatric Blood & Cancer 05/2004; 42(4):373-9. · 1.89 Impact Factor
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New England Journal of Medicine 04/2004; 350(13):1364-5. · 53.30 Impact Factor
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ABSTRACT: Voriconazole is a novel antifungal triazole that undergoes extensive oxidative metabolization involving several CYP450 isoenzymes. We report the case of a 14-year-old patient who received voriconazole concomitant with ciclosporin A as secondary antifungal prophylaxis after bone marrow transplantation. Temporary discontinuation of voriconazole due to worsening liver function tests (LFTs) resulted in a sudden drop of ciclosporin A trough levels in blood. Ciclosporin A trough levels returned to baseline following normalization of LFTs and re-institution of voriconazole. This report emphasizes the need for careful monitoring and dose adjustments of ciclosporin A in patients receiving concomitant voriconazole, and in whom voriconazole is discontinued in order to prevent subtherapeutic ciclosporin A levels with the potential consequence of graft-versus-host disease.
Journal of Antimicrobial Chemotherapy 02/2004; 53(1):113-4. · 5.07 Impact Factor
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CARS 2004. Computer Assisted Radiology and Surgery. Proceedings of the 18th International Congress and Exhibition, Chicago, USA, June 23-26, 2004; 01/2004
