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Stefan S Bielack

Publications and source records attributed to Stefan S Bielack.

16 recordsLinked to original sources
PubMed2006

Current strategies of chemotherapy in osteosarcoma.

Osteosarcoma, the most common type of primary malignant tumour that develops in bone, can be classified into several different sub-types. While the majority of osteosarcomas are highly malignant, there are some low-grade variants. Since the introduction of chemotherapy into the multi-modal treatment regimen of high-grade osteosarcoma, its prognosis has impressively improved, with long-term survival being achieved in two-thirds of all patients. This review summarises current chemotherapeutic treatment strategies in classical osteosarcoma and also addresses the indication for chemotherapy in more unusual types and variants. It emphasises the need for treatment in specialised centres and within prospective, multi-institutional trials, amongst which EURAMOS1 and EURO-B.O.S.S are currently active in many European countries.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

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

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.

Adolescent↗
PubMed2005

Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma.

PURPOSE: The aims of this analysis were to investigate the clinical features of extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal therapy. METHODS: The co-operative osteosarcoma study-group database was searched for patients with extraskeletal osteosarcoma. Eligible patients were included in a retrospective analysis of patient, tumour and treatment related variables and outcome. As for conventional osteosarcoma, scheduled treatment included surgery and multi-agent chemotherapy. RESULTS: Seventeen eligible patients were identified with a median age of 44 years (range, 3-65 years). The thigh was the commonest tumour site. Two patients had a history of previous malignancies and two had primary metastases. Median follow-up was 3.2 years (range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete remission, 3 patients were alive with disease and 3 patients had died of their disease. Three-year overall actuarial and event-free survival rates were 77% and 56%, respectively. Patients with macroscopically complete surgical remission had an improved overall survival (P = 0.0004). CONCLUSIONS: The patients in this retrospective study had a surprisingly good survival rate. This may be due to the combination of multi-agent chemotherapy with surgery, and we recommend this approach in the treatment of ESOS.

Adolescent↗
PubMed2005

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.

Adolescent↗
PubMed2005

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

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.

Child, Preschool↗
PubMed2004

Prognostic relevance of increased angiogenesis in osteosarcoma.

PURPOSE: The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma. EXPERIMENTAL DESIGN: Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival. RESULTS: The median intratumoral MVD was 52 microvessels per 0.26-mm2 field area (interquartile range, 31-77 microvessels per 0.26-mm2 field area). At a median follow-up period of 3.5 years, patients with a high (>median) MVD had significantly higher 5- and 10-year overall survival rates (84%) than patients with low (< or =median) MVD (49%; P = 0.0029). Furthermore, increased relapse-free survival for patients with high MVD (P = 0.0064) was observed. In a subgroup analysis of 44 patients with primary high-grade central osteosarcoma of the extremities without primary metastases and good surgical remission, high MVD was associated with 5- and 10-year overall survival rates of 91% compared with 58% for low MVD (P = 0.034). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histologic grading scale of Salzer-Kuntschik) correlated significantly with a high MVD (P = 0.006). CONCLUSIONS: Increased angiogenesis is a prognostic indicator for higher survival and response rates to chemotherapy in patients with osteosarcoma. Thus, measurement of MVD might be useful in decisions selecting patients for future neoadjuvant treatment.

Adolescent↗
PubMed2004

Delaying surgery with chemotherapy for osteosarcoma of the extremities.

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.

Antineoplastic Agents↗
PubMed2003

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2003

Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2002

Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas.

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.

Adolescent↗
PubMed2002

Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group.

BACKGROUND: Due to the low incidence rate, the optimal strategy for the treatment of patients with spinal osteosarcoma is unknown. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Adolescent↗
PubMed2002

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.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

Adolescent↗