Publications by authors named "Herbert Jürgens"

8 Publications

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Recurrence of Ewing sarcoma: Is detection by imaging follow-up protocol associated with survival advantage?

Pediatr Blood Cancer 2018 07 26;65(7):e27011. Epub 2018 Feb 26.

University Hospital Muenster, Westphalian-Wilhelms University, Muenster, Germany.

Background: The Cooperative Ewing Sarcoma Study and the Late Effects Surveillance System of the Society for Paediatric Oncology and Haematology recommend a structured follow-up imaging protocol (FUIP) for patients with Ewing sarcoma (EwS) with decreasing frequency of imaging over the first 5 years. The present study aims to assess the effectiveness of the FUIP for EwS patients regarding survival after relapse.

Patients And Methods: A retrospective multicenter analysis on 160 eligible patients with EwS recurrence was performed. Potential survival differences following recurrence diagnosis between patients with protocol-detected and symptomatic relapse were investigated using the Kaplan-Meier method. Additional subgroup analyses were performed on the relapse type. Overall survival (OS) was calculated from diagnosis of relapse to last follow-up or death.

Results: In the multicenter analysis, recurrence was detected by FUIP in 77 of 160 patients (48%) and due to symptoms in 83 patients (52%). Regarding the entire study population, OS was significantly superior in patients with protocol-detected relapse compared to patients with symptomatic relapse (median, 2.4 vs. 1.2 years; P < 0.001). In the subgroup analyses, patients whose lung recurrences were detected by the FUIP experienced longer survival after recurrence than those whose recurrences were detected symptomatically (P = 0.023). In the 83 symptomatic patients, pain was the most prevalent symptom of relapse (72%).

Conclusion: FUIP may benefit survival in EwS relapse, especially in lung recurrence. Pain was the leading symptom of relapse.
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http://dx.doi.org/10.1002/pbc.27011DOI Listing
July 2018

Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning.

Br J Haematol 2015 Jun 27;169(5):711-8. Epub 2015 Mar 27.

CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.
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http://dx.doi.org/10.1111/bjh.13347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433436PMC
June 2015

Osteosarcoma: the COSS experience.

Cancer Treat Res 2009 ;152:289-308

Pädiatrie 5 (Onkologie, Hämatologie,Immunologie), Klinikum Stuttgart, Zentrum für Kinder- und Jugendmedizin-Olgahospital, Bismarckstr. 8, D-70176, Stuttgart, Germany.

COSS, the interdisciplinary Cooperative German-Austrian-Swiss Osteosarcoma Study Group, was founded in 1977 and has since registered some 3,500 bone sarcoma patients from over 200 institutions. For the purpose of the Pediatric and Adolescent Osteosarcoma Conference in Houston, March 2008, the outcomes of 2,464 consecutive patients with high-grade central osteosarcoma, who had been diagnosed between 1980 and 2005 and had been treated on neoadjuvant COSS protocols, were reviewed. Intended treatment had included surgery and multidrug chemotherapy, with high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide being used in most protocols. After a median follow-up of 7.31 years for 1,654 survivors, 5- and 10-year survival estimates were 0.748/0.695 for 2,017 patients with localized extremity tumors and 0.369/0.317 for 444 patients with axial tumors or/and primary metastases, respectively. Tumor response to preoperative chemotherapy was of independent prognostic significance. Over the years, there was a major shift from amputation towards limb-salvage. This development was least evident for patients below the age of 10. While survival expectancies improved from the first to the second half of the recruitment period, no further improvement was evident within the latter period. In the manuscript, the results described above are discussed based on the findings of the previous analyses of our group.
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http://dx.doi.org/10.1007/978-1-4419-0284-9_15DOI Listing
October 2010

Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients.

J Clin Oncol 2008 Sep;26(27):4385-93

Department of PaediatricHaematology/Oncology, University Children's Hospital Münster, Switzerland.

Purpose: 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.

Patients And Methods: 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).

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1200/JCO.2008.16.5720DOI Listing
September 2008

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

Pediatr Blood Cancer 2006 Nov;47(6):795-800

Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany.

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.
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http://dx.doi.org/10.1002/pbc.20719DOI Listing
November 2006

Dose intensity of chemotherapy for osteosarcoma and outcome in the Cooperative Osteosarcoma Study Group (COSS) trials.

Pediatr Blood Cancer 2006 Jul;47(1):42-50

Universitätskinderklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Münster, Germany.

Background: The prognostic relevance of dose intensity in the treatment of osteosarcoma is still under discussion. The aim of this study was to investigate whether higher dose intensities of chemotherapy correlated with better outcomes.

Procedure: This study contains 917 consecutive Cooperative Osteosarcoma Study Group (COSS) patients <40 years with primary, high-grade central, nonmetastatic osteosarcoma of the extremities, who were in complete remission at least until day 200 after the start of chemotherapy. All COSS-protocols were based on a uniform treatment concept of aggressive polychemotherapy and definitive surgery. Chemotherapy dose intensity in the first 200 days of treatment (DI200) and possible correlations to overall and event-free survival were investigated. The study focused on methotrexate, doxorubicin, cisplatin, and ifosfamide, which are considered to be the most active drugs against osteosarcoma. Multivariate analyses including well-known prognostic factors were added to complete this investigation.

Results: Until day 200, patients received 80.7 +/- 26.1 g/m2 methotrexate (MTX); 242 +/- 69 mg/m2 doxorubicin (DOX); 324 +/- 133 mg/m2 cisplatin (DDP); and 13.9 +/- 9.8 g/m2 ifosfamide (IFO) (mean +/- SD). Median follow-up from day 200 was 6.6 (0.02-22.1) years. There was no correlation between a higher DI200 of any one drug and better outcomes in uni- or multi-variate analyses. Total treatment intensity did not show such correlations either.

Conclusions: In an overall setting of intensive multidrug treatment of osteosarcoma, we could not prove that higher dose intensities correlate with better outcomes.
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http://dx.doi.org/10.1002/pbc.20608DOI Listing
July 2006

Concomitant Ewing sarcoma and acute lymphoblastic leukemia in a 5-year-old girl.

Pediatr Blood Cancer 2005 Nov;45(6):846-9

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

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.
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http://dx.doi.org/10.1002/pbc.20265DOI Listing
November 2005

Cryopreservation of sperm from adolescents and adults with malignancies.

J Androl 2004 Jul-Aug;25(4):586-92

Institute of Reproductive Medicine of the University, D-48129 Muenster, Germany.

Although cryopreservation of sperm is performed routinely in adults, only a small amount of information is available on its feasibility in adolescent patients with malignancies. Of 936 patients who were candidates for sperm cryopreservation, 851 (111 adolescents and 740 adults) were eligible for this retrospective analysis after excluding patients with relapses of the original or secondary cancers, known bitesticular lesions, or an unknown diagnosis. In general, patients were seen before initiation of treatment for malignancies. However, unilateral ablation of the testis was performed in 61% of patients with testicular cancer before cryopreservation of samples. Patients were grouped according to primary diagnosis and age. Measurements included testicular volume, semen analysis, and serum hormones (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and testosterone). The youngest patient with an ejaculate containing sperm was 13.5 years old. No significant differences in any investigated parameter could be detected for any diagnosis among the 111 adolescents (age, <20 years). In contrast, adult patients with testicular cancer showed higher FSH values and lower sperm concentrations than adult patients with lymphomas, leukemias, and bone cancers. Patients younger than 16 years had lower ejaculate volumes than men older than 25 years, and testosterone levels were higher in patients aged 20-29 years than in the youngest patient group. Cryopreservation of sperm can be performed in adolescent patients with overall success rates (defined as the observation of at least a single motile sperm after the thawing procedure) similar to those observed in adults and should be recommended even to oncological patients younger than 15 years, provided that these patients can produce a semen sample.
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http://dx.doi.org/10.1002/j.1939-4640.2004.tb02829.xDOI Listing
June 2005