| 1. |
- Whelan, Jeremy, et al.
(författare)
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High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma : Results of Euro-E.W.I.N.G.99 and Ewing-2008
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:31, s. 3110-3119
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Tidskriftsartikel (refereegranskat)abstract
- Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis >200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year eventfree survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel comparedwith VAI: HR, 0.64 (95%CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0%(95% CI, 60.2%to 76.6%) versus 56.7%(95%CI, 47.6%to 65.4%) and 60.7%(95%CI, 51.1%to 69.6%) versus 47.1%(95%CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%(95%CI, 54.4% to 73.5%) versus 55.6%(95%CI, 45.8%to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
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| 2. |
- Maximov, Alexander, et al.
(författare)
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Plateaued rotation symmetric boolean functions on odd number of variables
- 2005
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Ingår i: [Host publication title missing]. - 2877754030
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Konferensbidrag (refereegranskat)abstract
- The class of Rotation Symmetric Boolean Functions (RSBFs) has received serious attention in searching functions of cryptographic significance. These functions are invariant under circular translation of indices. In this paper we study such functions on odd number of variables and interesting combinatorial properties related to Walsh spectra of such functions are revealed. In particular we concentrate on plateaued functions (functions with three valued Walsh spectra) in this class and derive necessary conditions for existence of balanced rotation symmetric plateaued functions. As application of our result we theoretically show the non existence of 9-variable, 3-resilient RSBF with nonlinearity 240 that has been posed as an open question in FSE 2004. Further we show how one can make efficient search in the space of RSBFs based on our theoretical results and as example we complete the search for unbalanced 9-variable, 3rd order correlation immune plateaued RSBFs with nonlinearity 240.
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| 3. |
- Andersson, Jon, et al.
(författare)
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Tree cavity densities and characteristics in managed and unmanaged Swedish boreal forest
- 2018
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Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 33, s. 233-244
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Tidskriftsartikel (refereegranskat)abstract
- In forests worldwide, similar to 10-40% of bird and mammal species require cavities for nesting or roosting. Although knowledge of tree cavity availability and dynamics has increased during past decades, there is a striking lack of studies from boreal Europe. We studied the density and characteristics of cavities and cavity-bearing trees in three categories of forest in a north-Swedish landscape: clearcuts with tree retention, managed old (>100 years) forest, and unmanaged old forest. Unmanaged old forests had significantly higher mean density of cavities (2.4 +/- 2.2(SD) ha(-1)) than managed old forest (1.1 +/- 2.1 ha(-1)). On clearcuts the mean cavity density was 0.4 +/- 2.3 ha(-1). Eurasian aspen (Populus tremula) had a higher probability of containing excavated cavities than other tree species. There was a greater variety of entrance hole shapes and a higher proportion of cavities with larger entrances in old forest than on clearcuts. Although studies of breeding success will be necessary to more accurately assess the impact of forest management on cavity-nesting birds, our results show reduced cavity densities in managed forest. To ensure future provision of cavities, managers should retain existing cavity-bearing trees as well as trees suitable for cavity formation, particularly aspen and dead trees.
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| 4. |
- Gaspar, Nathalie, et al.
(författare)
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Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:27, s. 140-3036
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Forskningsöversikt (refereegranskat)abstract
- Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.
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| 5. |
- Hero, Barbara, et al.
(författare)
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Genomic Profiles of Neuroblastoma Associated With Opsoclonus Myoclonus Syndrome
- 2018
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Ingår i: Journal of Pediatric Hematology/Oncology. - 1077-4114. ; 40:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Opsoclonus myoclonus syndrome (OMS), often called "dancing eyed syndrome," is a rare neurological condition associated with neuroblastoma in the majority of all childhood cases. Genomic copy number profiles have shown to be of prognostic significance for neuroblastoma patients. The aim of this retrospective multicenter study was to analyze the genomic copy number profiles of tumors from children with neuroblastoma presenting with OMS at diagnosis. In 44 cases of neuroblastoma associated with OMS, overall genomic profiling by either array-comparative genomic hybridization or single nucleotide polymorphism array proved successful in 91% of the cases, distinguishing tumors harboring segmental chromosome alterations from those with numerical chromosome alterations only. A total of 23/44 (52%) tumors showed an segmental chromosome alterations genomic profile, 16/44 (36%) an numerical chromosome alterations genomic profile, and 1 case displayed an atypical profile (12q amplicon). No recurrently small interstitial copy number alterations were identified. With no tumor relapse nor disease-related deaths, the overall genomic profile was not of prognostic impact with regard to the oncological outcome in this series of patients. Thus, the observation of an excellent oncological outcome, even for those with an unfavorable genomic profile of neuroblastoma, supports the hypothesis that an immune response might be involved in tumor control in these patients with OMS.
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| 6. |
- Ladenstein, Ruth, et al.
(författare)
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Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial.
- 2010
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; Jul 1, s. 3284-3291
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept. PATIENTS AND METHODS From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT). Results After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score /= 5 (70 patients; P < .0001). CONCLUSION PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.
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| 7. |
- Le Deley, Marie-Cécile, et al.
(författare)
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Cyclophosphamide Compared With Ifosfamide in Consolidation Treatment of Standard-Risk Ewing Sarcoma: Results of the Randomized Noninferiority Euro-EWING99-R1 Trial.
- 2014
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 32:23, s. 2440-2448
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Tidskriftsartikel (refereegranskat)abstract
- Relative efficacy and toxicity of cyclophosphamide compared with ifosfamide are debatable. The Euro-EWING99-R1 trial asked whether cyclophosphamide may replace ifosfamide in combination with vincristine and dactinomycin (vincristine, dactinomycin, and cyclophosphamide [VAC] v vincristine, dactinomycin, and ifosfamide [VAI]) after an intensive induction chemotherapy containing vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in standard-risk localized disease (NCT00020566).
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| 8. |
- Schleiermacher, Gudrun, et al.
(författare)
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Emergence of New ALK Mutations at Relapse of Neuroblastoma
- 2014
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology: JCO. - 0732-183X .- 1527-7755. ; 32:25, s. 2727-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. Methods We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). Conclusion In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
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