| Autor(en) |
Titel |
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| Oberlin O, Rey A, Anderson J, Carli M, Raney R, Treuner J, Stevens M |
Treatment of orbital rhabdomyosarcoma. |
J Clin Oncol 2001, 19: 197 |
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| Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M |
The tumor-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. |
Clin Cancer Res 2004, 10: 4307 |
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| Oberthuer A, Berthold F, Warnat P, Hero B, Kahlert Y, Spitz R, Ernestus K, König R, Haas S, Eils R, Schwab M, Brors B, Westermann F, Fischer M |
Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2006, 24: 5070 |
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| PURPOSE: To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease. PATIENTS AND METHODS: Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States. RESULTS: The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]). CONCLUSION: Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials. |
| Oberthuer A, Warnat P, Kahlert Y, Westermann F, Spitz R, Brors B, Hero B, Eils R, Schwab M, Berthold F, Fischer M |
Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease. [+] |
Cancer letters 2007, 250: 250 |
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| Currently, Pubmed lists 385 marker genes for neuroblastoma outcome. Using a customized neuroblastoma-microarray, we evaluated the prognostic impact of the gene-expression pattern of 349 of these candidates (90.6%) in 127 neuroblastoma patients with divergent outcome. By significance analysis of microarrays (SAM) and both uncorrected and Bonferroni-corrected ANOVA, 166/349 (47.5%), 218/349 (62.5%) and 128/349 (36.4%) candidates showed significant differential expression between patients with contrasting outcome. By Prediction Analysis for Microarrays (PAM), a 38-gene-classifier was derived from all markers, which classified patients outcome with an overall accuracy of 78.5%. However, patients with unfavorable outcome of MYCN non-amplified disease were largely misclassified (accuracy: 35%), suggesting that these courses are not identified by current marker genes. |
| Oberthuer A, Kaderali L, Kahlert Y, Hero B, Westermann F, Berthold F, Brors B, Eils R, Fischer M |
Subclassification and individual survival time prediction from gene expression data of neuroblastoma patients by using CASPAR. [+] |
Clinical cancer research : an official journal of the American Association for Cancer Research 2008, 14: 6590 |
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| PURPOSE: To predict individual survival times for neuroblastoma patients from gene expression data using the cancer survival prediction using automatic relevance determination (CASPAR) algorithm. EXPERIMENTAL DESIGN: A first set of oligonucleotide microarray gene expression profiles comprising 256 neuroblastoma patients was generated. Then, CASPAR was combined with a leave-one-out cross-validation to predict individual times for both the whole cohort and subgroups of patients with unfavorable markers, including stage 4 disease (n = 67), unfavorable genetic alterations, intermediate-risk or high-risk stratification by the German neuroblastoma trial, and patients predicted as unfavorable by a recently described gene expression classifier (n = 83). Prediction accuracy of individual survival times was assessed by Kaplan-Meier analyses and time-dependent receiver operator characteristics curve analyses. Subsequently, classification results were validated in an independent cohort (n = 120). RESULTS: CASPAR separated patients with divergent outcome in both the initial and the validation cohort [initial set, 5y-OS 0.94 +/- 0.04 (predicted long survival) versus 0.38 +/- 0.17 (predicted short survival), P < 0.0001; validation cohort, 5y-OS 0.94 +/- 0.07 (long) versus 0.40 +/- 0.13 (short), P < 0.0001]. Time-dependent receiver operator characteristics analyses showed that CASPAR-predicted individual survival times were highly accurate (initial set, mean area under the curve for first 10 years of overall survival prediction 0.92 +/- 0.04; validation set, 0.81 +/- 0.05). Furthermore, CASPAR significantly discriminated short (<5 years) from long survivors (>5 years) in subgroups of patients with unfavorable markers with the exception of MYCN-amplified patients (initial set). Confirmatory results with high significance were observed in the validation cohort [stage 4 disease (P = 0.0049), NB2004 intermediate-risk or high-risk stratification (P = 0.0017), and unfavorable gene expression prediction (P = 0.0017)]. CONCLUSIONS: CASPAR accurately forecasts individual survival times for neuroblastoma patients from gene expression data. |
| Oberthuer A, Theissen J, Westermann F, Hero B, Fischer M |
Molecular characterization and classification of neuroblastoma. [+] |
Future oncology (London, England) 2009, 5: 625 |
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| For many decades, neuroblastoma has remained a challenging disease for both clinicians and researchers. Now, techniques that efficiently specify both comprehensive genetic and gene-expression alterations of neuroblastoma tumors have provided molecular markers that indicate tumor behavior and patient outcome with very high accuracy. Once the anticipated value of these markers has been confirmed in ongoing studies, patients may profit from more accurate risk assessment by integrating these markers into clinical routine. Moreover, disclosing further tumor-initiating events, such as the recently revealed oncogenic mutations of ALK, will further promote the elucidation of the genetic etiology of the disease. Together with recent information on altered signaling pathways in aggressively growing tumors, this knowledge will help to establish therapeutic strategies specifically targeting molecular key factors of neuroblastoma tumor progression. |
| Oda Y, Jürgens H, Roessner A |
Expression of multidrug resistance-associated protein gene in Ewing's sarcoma and malignant peripheral neuroectodermal tumor of bone. |
J Cancer Res Clin Oncol 1997, 123: 237 |
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| Okcu M, Munsell M, Treuner J, Mattke A, Pappo A, Cain A, Ferrari A, Casanova M, Ozkan A, Raney B |
Synovial sarcoma of childhood and adolescence. |
J Clin Oncol 2003, 21: 1602 |
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| Oommen PT, Linden T, Romahn A, Bucsky P |
UICC-2002 TNM-classification is not suitable for differentiated thyroid carcinoma in children and adolescent - interim results of GPOH-MET 97 trial. |
Pediatric Blood & Cancer 2005, 45: 482 P.D. 111 |
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| Oommen PT, Romahn A, Linden T, Frühwald MC, Bucsky P |
UICC-2002 TNM classification is not suitable for differentiated thyroid cancer in children and adolescents. [+] |
Pediatr Blood Cancer 2008, 50: 1159-62. |
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| BACKGROUND: Recently the UICC-TNM classification for differentiated thyroid cancer (DTC) was changed neglecting the special circumstances for children affected by the disease. While the 1997 TNM classification grouped tumours |
| Opocher E, Kremer LC, Da Dalt L, van de Wetering MD, Viscardi E, Caron HN, Perilongo G |
Prognostic factors for progression of childhood optic pathway glioma: a systematic review. [+] |
European journal of cancer 2006, 42: 1807 |
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| A systematic literature review was carried out to evaluate best existing evidence on prognostic factors for progression of childhood optic pathway glioma. Databases were searched for relevant articles and articles selected independently by two authors. Information about study design, population, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed. A total of 23 articles met the inclusion criteria. Many studies had important methodological limitations, regarding external and internal validity. Eleven studies evaluated possible prognostic factors in a multivariate analysis. Three high-quality studies indicated age<1 year as an independent prognostic factor for a worse progression-free survival. Three studies with multivariate analysis, including one high-quality study, found that children with neurofibromatosis type 1 (NF-1) have a better progression-free survival than those without NF-1. Two studies with multivariate analysis found tumour site to be a prognostic factor, both with some methodological limitations. In conclusion, this systematic review demonstrates that only a few of the prognostic factors proposed have been proven to be clinically relevant. Age<1 year is a clear and independent prognostic factor for progression-free survival. Other prognostic factors, such as NF-1, tumour site and others, are suggested, but are still without solid evidence and need further high-quality studies to be clearly proven. |
| Orr LC, Fleitz J, McGavran L, Wyatt-Ashmead J, Handler M, Foreman NK |
Cytogenetics in pediatric low-grade astrocytomas. |
Med Pediatr Oncol 2002, 38: 173 |
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| Oschlies I, Klapper W, Zimmermann M, Krams M, Wacker HH, Burkhardt B, Harder L, Siebert R, Reiter A, Parwaresch R |
Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Frankfurt-Münster) Multicenter Trial. |
Blood 2006, 107: 4047 |
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| Ostertag CB |
Stereotactic interstitial radiotherapy for brain tumors. |
J Neurosurg Sci 1989, 33: 83 |
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| Ottinger HD et al. |
Empfehlungen zur immungenetischen Spenderauswahl für die allogene Transplantation von Knochenmark und peripheren Blutstammzellen. |
Leitlinien und Empfehlungen der Deutschen Gesellschaft für Immungenetik 1999 |
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| Otte JB, Pritchard J, Aronson DC, Brown J, Czauderna P, Maibach R, Perilongo G, Shafford E, Plaschkes J, International Society of Pediatric Oncology (SIOP) |
Otte JB, Pritchard J, Aronson DC, et al.: Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. [+] |
Pediatr Blood Cancer 2004, 42: 74-83. |
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| BACKGROUND: For hepatoblastoma (HB) that remains unresectable by partial hepatectomy after chemotherapy, total hepatectomy with orthotopic liver transplantation (LTX) has been advocated as the best treatment option. The role of LTX in the overall management of HB is still, however, unclear.
PROCEDURE: The results of LTX from the first study of HB by the International Society of Pediatric Oncology, SIOPEL-1, were analyzed. In addition, the world experience of LTX for HB was extensively reviewed. Twelve patients in the SIOPEL-1 study underwent a LTX. Median (range) follow-up at Dec. 31, 2001 was 117 months (52-125) since LTX.
RESULTS: Overall survival at 10 years post-LTX was 85% for the seven children who received a "primary LTX" and 40% for the 5 children who underwent a "rescue LTX" after previous partial hepatectomy. In the world experience (147 cases), the overall survival rate at 6 year post-LTX was 82% for 106 patients who received a "primary LTX" and 30% for 41 patients who underwent a "rescue LTX." Multivariate analysis of patients undergoing primary LTX showed that only macroscopic venous invasion had a significant impact (P-value: 0.045 with a hazard ratio of 2.96) on overall survival.
CONCLUSIONS: Orthotopic LTX has added a new dimension to the treatment of HB unresectable by partial hepatectomy. Because of the rarity of the disease and to optimize results, children with extensive HB should be treated in centers with surgical expertise in pediatric major liver resection and LTX, in close collaboration with pediatric oncologists, radiologists, and histopathologists. |
| Ouachée-Chardin M, Elie C, de Saint Basile G, Le Deist F, Mahlaoui N, Picard C, Neven B, Casanova JL, Tardieu M, Cavazzana-Calvo M, Blanche S, Fischer A |
Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. [+] |
Pediatrics 2006, 117:e743 |
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| OBJECTIVES: Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically determined disorder characterized by the early onset of fever, hepatosplenomegaly, central nervous system disease, thrombocytopenia, coagulation disorders, and hemophagocytosis. It is caused by genetic defects that impair T cell-mediated and natural cytotoxicity. Chemotherapy- or immunotherapy-based treatments can achieve remission. Hematopoietic stem cell transplantation (HSCT), however, is the only curative option, but optimal modalities and long-term outcome are not yet well known. METHODS: We retrospectively analyzed the outcome of HSCT that was performed in 48 consecutive patients who had FHLH and were treated in a single center between 1982 and 2004. RESULTS: The overall survival was 58.5% with a median follow-up of 5.8 years and extending to 20 years. A combination of active disease and haploidentical HSCT had a poor prognosis because in this situation, HLH disease is more frequently associated with graft failure. Twelve patients received 2 transplants because of graft failure (n = 7) or secondary graft loss that led to HLH relapse (n = 5). Transplant-related toxicity essentially consisted in veno-occlusive disease, which occurred in 28% of transplants and was associated with young age, haploidentical transplantation, and the use of antithymocyte globulin (ATG) in the conditioning regimen. A sustained remission was achieved in all patients with a donor chimerism > or = 20% of leukocytes. Long-term sequelae were limited, because only 2 (7%) of 28 patients experienced a mild neurologic disorder. CONCLUSIONS: This survey demonstrates the long-term efficacy of HSCT as a cure of FHLH. HSCT preserves quality of life. It shows that HSCT should be performed as early as a complete remission has been achieved. Additional studies are required to improve the procedure and reduce its toxic effects. |
| Ozaki T, Lindner N, Hoffmann C, Hillmann A, Rödl R, Blasius S, Link T, Winkelmann W, Jürgens H |
Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study. |
Eur J Cancer 1995, 31A: 2284 |
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| Ozaki T, Hillmann A, Hoffmann C, Rübe C, Blasius S, Dunst J, Jürgens H, Winkelmann W |
Significance of surgical margin on the prognosis of patients with Ewing's sarcoma. A report from the Cooperative Ewing's Sarcoma Study. |
Cancer 1996, 78: 892 |
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| Ozaki T, Hillmann A, Hoffmann C, Rübe C, Blasius S, Dunst J, Treuner J, Jürgens H, Winkelmann W |
Ewing's sarcoma of the femur - Prognosis in 69 patients treated by the CESS group. |
Acta Orthop Scand 1997, 68: 20 |
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| Ozaki T, Hillmann A, Rübe C, Rödl R, Hein M, Hoffmann C, Blasius S, Jürgens H, Winkelmann W |
The impact of intraoperative brachytherapy on surgery of Ewing's sarcoma. |
J Cancer Res Clin Oncol 1997, 123: 53 |
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| Ozaki T, Winkelmann W, Willich N, Jürgens H |
Treatment of Ewing's sarcoma in the Cooperative Ewing's Sarcoma Study group. |
J Orthop Sci 1997, 2: 180 |
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| Ozaki T, Paulussen M, Poremba C, Brinkschmidt C, Rerin J, Ahrens S, Hoffmann C, Hillmann A, Wai D, Schaefer K, Boecker W, Jürgens H, Winkelmann W, Dockhorn-Dworniczak B |
Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors. |
Genes Chromosomes Cancer 2001, 32: 164 |
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| Ozaki T, Flege S, Liljenqvist U, Hillmann A, Delling G, Salzer-Kuntschik M, Jürgens H, Kotz R, Winkelmann W, Bielack S |
Osteosarcoma of the spine. |
Cancer 2002, 94: 1069 |
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| Ozaki T, Schaefer K, Wai D, Buerger H, Flege S, Lindner N, Kevric M, Diallo R, Bankfalvi A, Brinkschmidt C, Jürgens H, Winkelmann W, Dockhorn-Dworniczak B, Bielack S, Poremba C |
Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas. |
Int J Cancer 2002, 102: 355 |
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| Ozaki T, Flege S, Kevric M, Lindner N, Maas R, Delling G, Schwarz R, von Hochstetter A, Salzer-Kuntschik M, Berdel W, Jürgens H, Exner G, Reichardt P, Mayer-Steinacker R, Ewerbeck V, Kotz R, Winkelmann W, Bielack S |
Osteosarcoma of the pelvis. |
J Clin Oncol 2003, 21: 334 |
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