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11.
Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. 总被引:4,自引:0,他引:4
Leo Kager Andreas Zoubek Ulrike P?tschger 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 《Journal of clinical oncology》2003,21(10):2011-2018
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. 相似文献
12.
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 《Journal of clinical oncology》2003,21(2):334-341
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. 相似文献
13.
G. Hempel Sebastian Krümpelmann Antje May-Manke Barbara Hohenlöchter Gottfried Blaschke Heribert Jürgens Joachim Boos 《Cancer chemotherapy and pharmacology》1997,40(1):45-50
To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral
administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m2 Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and
its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and
analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUCTrofo:AUCIfo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUCIfo:AUCCyclo 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechloroethylifosfamide in varying
quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose.
Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo
can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting
agent for oral chemotherapy.
Received 21 July 1996 / Accepted: 11 November 1996 相似文献
14.
Katrin Lamszus Marc A Brockmann Carmen Eckerich Peter Bohlen Chad May Ulrich Mangold Regina Fillbrandt Manfred Westphal 《Clinical cancer research》2005,11(13):4934-4940
PURPOSE: Inhibition of angiogenesis can influence tumor cell invasion and metastasis. We previously showed that blockade of vascular endothelial growth factor receptor-2 (VEGFR-2) with the monoclonal antibody DC101 inhibited intracerebral glioblastoma growth but caused increased tumor cell invasion along the preexistent vasculature. In the present study, we attempted to inhibit glioma cell invasion using a monoclonal antibody against the epidermal growth factor receptor (EGFR), which in the context of human glioblastomas, has been implicated in tumor cell invasion. In addition, we analyzed whether blockade of vascular endothelial (VE)-cadherin as a different antiangiogenic target could also inhibit glioblastoma angiogenesis and growth. EXPERIMENTAL DESIGNS: Nude mice who received intracerebral glioblastoma xenografts were treated using monoclonal antibodies against VEGFR-2 (DC101), EGFR (C225), and VE-cadherin (E4G10) either alone or in different combinations. RESULTS: Increased tumor cell invasion provoked by DC101 monotherapy was inhibited by 50% to 66% by combined treatment with C225 and DC101. C225 inhibited glioblastoma cell migration in vitro, but had no effect on the volume of the main tumor mass or on tumor cell proliferation or apoptosis in vivo, either alone or in combination with DC101. The anti-VE-cadherin monoclonal antibody E4G10 was a weaker inhibitor of tumor angiogenesis and growth than DC101, and also caused a weaker increase in tumor cell invasion. CONCLUSIONS: Inhibition of angiogenesis achieved by blocking either VEGFR-2 or VE-cadherin can cause increased glioma cell invasion in an orthotopic model. Increased tumor cell invasion induced by potent inhibition of angiogenesis with DC101 could be inhibited by simultaneous blockade of EGFR. 相似文献
15.
Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). 总被引:4,自引:0,他引:4
Beate Kempf-Bielack Stefan S Bielack Heribert Jürgens Detlev Branscheid Wolfgang E Berdel G Ulrich Exner Ulrich G?bel Knut Helmke Gernot Jundt Hartmut Kabisch Mathias Kevric Thomas Klingebiel Rainer Kotz Rainer Maas Rudolf Schwarz Michael Semik J?rn Treuner Andreas Zoubek Kurt Winkler 《Journal of clinical oncology》2005,23(3):559-568
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. 相似文献
16.
Shqipdona Lahu Peter Bristot Senta Gewalt Alexander Goedel Daniele Giacoppo Stefanie Schüpke Heribert Schunkert Adnan Kastrati Nikolaus Sarafoff 《Journal of atherosclerosis and thrombosis》2022,29(7):1001
Aim: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an ongoing debate and novel data has emerged. The aim of this meta-analysis was to assess outcomes of short vs. control DAPT duration. In addition, the role of single antiplatelet therapy (SAPT) after DAPT with either aspirin or P2Y12 inhibitor monotherapy was analyzed. Methods: The authors searched MEDLINE and Cochrane databases and proceedings of international meetings for randomized controlled trials (RCT) comparing ≤ 3 months with ≥ 6 months DAPT after DES implantation. The primary and co-primary outcomes of interest were definite or probable stent thrombosis (ST) and bleeding. In addition, we performed an analysis on studies who continued with either aspirin or P2Y12 monotherapy after DAPT. Results: 9 RCTs comprising 41,864 patients were included and we analyzed a short DAPT duration of median 1.5 months vs. 12.1 months in the control group. The risk for ST was similar with short vs. control DAPT duration (0.5 vs. 0.5%; hazard ratio 1.17[95% CI 0.89-1.54];p=0.26). Bleeding was significantly reduced with short vs. control DAPT duration (1.9 vs. 3.0%; 0.65[0.54-0.77];p<0.0001). ST was not different between short vs. control DAPT duration in the analysis of the 4 RCTs who continued with aspirin after DAPT and the 5 P2Y12 RCTs, respectively, and no heterogeneity was detected (p=0.861). Bleeding was also reduced with short vs. control DAPT in both the aspirin (1.2 vs. 1.7%; 0.71[0.51-0.99];p=0.04) and P2Y12 inhibitor studies (2.1 vs. 3.4%; 0.62[0.47-0.80];p=0.0003) and no heterogeneity was detected (p=0.515). Conclusions: Our meta-analysis shows that short DAPT ≤ 3 months followed by SAPT reduces bleeding and is not associated with an increase in ST. The results were consistent within the aspirin and P2Y12 SAPT studies. 相似文献
17.
Background: Sorbents have been shown to adsorb iodinated radiocontrast media. Objective: In this study we describe a simple method to compare various sorbents in terms of capacity to adsorb radiocontrast media. Methods: Iodixanol solution was injected into columns filled with three types of sorbent at filtration velocities of increasing magnitude. Two variables of interest - contrast removal rate and matched iodine retention (MIR) - were calculated to measure the adsorption efficiency and the mass of contrast iodine adsorbed versus sorbent used, respectively. Results: The highest contrast removal and MIR for Porapak Q, CST 401 and Amberlite XAD4 were 41, 38 and 16% (p = 0.22 and 0.0005 for comparisons between Porapak Q-CST 401 and CST 401-Amberlite XAD4) and 0.060, 0.055 and 0.024, respectively (p = 0.18 and 0.0008). Extrapolation to a clinical scenario may suggest that removal of 8 ml iodixanol could be achieved by masses of sorbents of 43, 47 and 107 g, respectively. Conclusion: In this study we set a benchmark for comparing the radiocontrast-adsorbing efficiency of polymer sorbents during first-pass experiments, using a readily available methodology. 相似文献
18.
19.
The early microvascular consequences of streptozotocin-induced diabetes in adult mice were evaluated. Streptozotocin (200 mg/kg) was used to induce diabetes at age 22–24 weeks and the animals were studied at age 32–36 weeks when microvascular disturbances are consistently present. The arterioles within the cremasteric muscle of AOD mice have a significantly (P < 0.05) reduced inner diameter and vessel wall cross-sectional area. In normal animals, inner vessel diameter and vessel wall characteristics remained essentially constant from week 22–36 of life. The average intercapillary distance in passive preparations is 20.6 ± 0.4 μm in normal mice compared to 25.9 ± 0.3 μm in diabetic mice; a loss of capillaries appeared to occur in diabetics but no substantial change in number of arterioles occurred. The ability of vessels to dilate from the innervated to passive state is proportionately equal to or greater than normal in the AOD mice but the actual diameters of innervated and passive arterioles are smaller than normal. The data are interpreted to indicate that an early microvascular manifestation of AOD in mice is an impairment of the vessel wall and a loss of capillaries. However, resting blood flow is only marginally decreased in the early phase of the onset of diabetes in adult mice. 相似文献
20.
MP2C, a plant protein phosphatase 2C, functions as a negative regulator of mitogen-activated protein kinase pathways in yeast and plants 下载免费PDF全文