Stefan S Bielack

Publications (29)308.4 Total impact

• Article: Delaying surgery with chemotherapy for osteosarcoma of the extremities.

  Stefan S Bielack, Jan-Nicolas Machatschek, Silke Flege, Heribert Jürgens
  [show abstract] [hide abstract]
  ABSTRACT: Osteosarcoma is the most frequent primary cancer of bone. When treated by surgery alone, it is almost invariably followed by metastatic dissemination and death. This dismal prognosis can be improved dramatically by including chemotherapy in an interdisciplinary regimen. Today, two-thirds of patients with localised extremity primaries can achieve long-term survival with such intensive multimodal therapy. This article provides a summary overview of current pharmacotherapy in osteosarcoma of the extremities, focussing on the approach of preoperative 'neoadjuvant' chemotherapy and thus, the potential benefits and pitfalls of delaying surgery. Prospective, multi-institutional trials are essential in guaranteeing that as many patients as possible can benefit from modern, efficacious interdisciplinary therapeutic regimens and that further progress can be made.
  Expert Opinion on Pharmacotherapy 07/2004; 5(6):1243-56. · 3.20 Impact Factor
• Article: A patient with two Ewing's sarcomas with distinct EWS fusion transcripts.

  Stefan S Bielack, Michael Paulussen, Gabriele Köhler
  New England Journal of Medicine 04/2004; 350(13):1364-5. · 53.30 Impact Factor
• Article: Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

  Leo Kager, Andreas Zoubek, Ulrike Pötschger, Ulrike Kastner, Silke Flege, Beate Kempf-Bielack, Detlev Branscheid, Rainer Kotz, Mechthild Salzer-Kuntschik, Winfried Winkelmann, Gernot Jundt, Hartmut Kabisch, Peter Reichardt, Heribert Jürgens, Helmut Gadner, Stefan S Bielack
  [show abstract] [hide abstract]
  ABSTRACT: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.
  Journal of Clinical Oncology 06/2003; 21(10):2011-8. · 18.37 Impact Factor
• Article: Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

  Toshifumi Ozaki, Silke Flege, Matthias Kevric, Norbert Lindner, Rainer Maas, Günter Delling, Rudolf Schwarz, Arthur R von Hochstetter, Mechthild Salzer-Kuntschik, Wolfgang E Berdel, Heribert Jürgens, G Ulrich Exner, Peter Reichardt, Regine Mayer-Steinacker, Volker Ewerbeck, Rainer Kotz, Winfried Winkelmann, Stefan S Bielack
  [show abstract] [hide abstract]
  ABSTRACT: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.
  Journal of Clinical Oncology 01/2003; 21(2):334-41. · 18.37 Impact Factor
• Article: Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas.

  Toshifumi Ozaki, Karl-Ludwig Schaefer, Daniel Wai, Horst Buerger, Silke Flege, Norbert Lindner, Matthias Kevric, Raihanatou Diallo, Agnes Bankfalvi, Christian Brinkschmidt, Heribert Juergens, Winfried Winkelmann, Barbara Dockhorn-Dworniczak, Stefan S Bielack, Christopher Poremba
  [show abstract] [hide abstract]
  ABSTRACT: Osteosarcomas are the most frequent bone sarcomas. The molecular chromosomal aberrations in osteosarcomas were analyzed by comparative genomic hybridization (CGH). We studied 47 frozen tumors (41 primary samples, 6 relapses) in osteosarcoma patients registered in the Cooperative Osteosarcoma Study (COSS) protocol. Genomic imbalances were detected in 40 of 41 primary tumors and 6 of 6 relapsed tumors. Gains were more frequent than losses (ratio of 1.3:1). The median number of changes was 16 and 12 in primary and relapsed osteosarcomas, respectively. The median number of aberrations in primary high-grade osteosarcomas (17.0) was significantly higher than in low- or intermediate-grade osteosarcoma subtypes (3.0) (p = 0.038). The most frequent gains included 8q, 1p21-p31 and 1q21-q24, and the most frequent losses were 10q, 5q and 13q. High-level gains were observed on 8q23-q24, 17p13 and 1q21-q24. A gain of 19p (p < 0.001) or loss of 9p (p = 0.027) was more frequent in poor responders than in good responders. Univariate analysis revealed that patients with primary metastases (p = 0.002), poor histologic responses (p = 0.005), high-level gains of 19p (p = 0.012) or losses of 13q14 (p = 0.042) had significantly lower event-free survival (EFS), whereas patients with a loss of 5q (p = 0.007) or a loss of 10q21-22 (p = 0.017) had significantly higher EFS than patients without these aberrations. Multivariate analysis demonstrated that primary metastasis, loss of 13q14 and loss of 5q were independent prognostic factors. The findings of our study seem to be useful for evaluating the prognosis of patients and may finally lead to treatment strategies based on genetic background of osteosarcoma.
  International Journal of Cancer 12/2002; 102(4):355-65. · 5.44 Impact Factor
• Source

  Available from: ascopubs.org

  Article: High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases.

  Christine Franzius, Andreas Schuck, Stefan S Bielack
  Journal of Clinical Oncology 05/2002; 20(7):1953-4. · 18.37 Impact Factor
• Article: Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group.

  Toshifumi Ozaki, Silke Flege, Ulf Liljenqvist, Axel Hillmann, Günter Delling, Mechthild Salzer-Kuntschik, Heribert Jürgens, Rainer Kotz, Winfried Winkelmann, Stefan S Bielack
  [show abstract] [hide abstract]
  ABSTRACT: Due to the low incidence rate, the optimal strategy for the treatment of patients with spinal osteosarcoma is unknown. Twenty-two patients with osteosarcoma of the spine (15 with tumors of the sacrum and 7 with tumors at other sites) who received chemotherapy according to the Cooperative Osteosarcoma Study Group protocol were analyzed. Six patients presented with metastasis, and 16 patients had no evidence of metastasis at the time of entry into the protocol. Of 12 patients who underwent excision of their tumors, 2 patients underwent wide excision, 3 patients underwent marginal excision, and 7 patients underwent intralesional excision. Eight patients received irradiation: Six patients received conventional radiotherapy only, one patient received neutron beam therapy, and one patient received samarium-153-ethylene diamine tetramethylene phosphonate therapy. Follow-up ranged between 24 months and 105 months (median, 47 months). The median survival was 23 months, and three patients have survived without disease for > 6 years. Patients with primary metastases (P = 0.004), large tumors (P = 0.010), and sacral tumors (P = 0.048) had lower overall survival compared with patients who had no metastasis, small tumors, and nonsacral tumors, respectively. There was a significant difference in overall survival between 5 patients who underwent either wide or marginal surgery and 17 patients who underwent either intralesional surgery or no surgery (P = 0.033). Among 17 patients who underwent no surgery or intralesional surgery, overall survival tended to be better in 7 patients who received irradiation compared with the overall survival in 10 patients who did not receive irradiation (P = 0.059). Patients with metastases, a large tumors, and sacral tumors had a poor prognosis in the current study with small numbers of patients. Wide or marginal excision of the tumor improved survival. Patients with osteosarcoma of the spine should be treated with a combination of chemotherapy and at least marginal excision for those with surgically accessible tumors. Postoperative radiotherapy may be beneficial.
  Cancer 03/2002; 94(4):1069-77. · 4.77 Impact Factor
• Article: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols.

  Stefan S Bielack, Beate Kempf-Bielack, Günter Delling, G Ulrich Exner, Silke Flege, Knut Helmke, Rainer Kotz, Mechthild Salzer-Kuntschik, Matthias Werner, Winfried Winkelmann, Andreas Zoubek, Heribert Jürgens, Kurt Winkler
  [show abstract] [hide abstract]
  ABSTRACT: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival > or = 40, 41.6%; < 40, 60.2%; P =.012), tumor site (axial, 29.2%; limb, 61.7%; P <.0001), and primary metastases (yes, 26.7%; no, 64.4%; P <.0001), and for extremity osteosarcomas, also size (> or = one third, 52.5%; < one third, 66.7%; P <.0001) and location within the limb (proximal, 49.3%; other, 63.9%; P <.0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P <.0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P <.0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors. Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.
  Journal of Clinical Oncology 02/2002; 20(3):776-90. · 18.37 Impact Factor
• Article: Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma

  Stefan S. Bielack, Rudolf Erttmann, Guido Looft, Christine Purfürst, Günther Delling, Kurt Winkler, Günther Landbeck
  [show abstract] [hide abstract]
  ABSTRACT: Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Turmors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.
  Cancer Chemotherapy and Pharmacology 10/1989; 24(6):376-380. · 2.83 Impact Factor