| 1. |
- Adrian-Martinez, S., et al.
(författare)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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| 2. |
- Dantonello, Tobias M., et al.
(författare)
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Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1267-1273
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Tidskriftsartikel (refereegranskat)abstract
- Background Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Methods Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Results Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 +/- 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection+radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 +/- 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Conclusion Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment.
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| 3. |
- Fojecki, Grzegorz, et al.
(författare)
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Consultation on UTUC, Stockholm 2018 aspects of diagnosis of upper tract urothelial carcinoma
- 2019
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Ingår i: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 37:11, s. 2271-2278
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To summarize knowledge on upper urinary tract carcinoma (UTUC) regarding diagnostic procedures, risk factors and prognostic markers.Methods: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC in Stockholm, September 2018.Results: Tumor stage and grade are the most important prognostic factors. CT urography (CTU) including corticomedullary phase is the preferred imaging modality. A clear tumor on CTU in combination with high-grade UTUC in urine cytology identifies high-risk UTUC, and in some cases indirect staging can be obtained. Bladder urine cytology has limited sensitivity, and in most cases ureterorenoscopy (URS) with in situ samples for cytology and histopathology are mandatory for exact diagnosis. Image-enhancing techniques, Image S1 and narrow-band imaging, may improve tumor detection at URS. Direct confocal laser endomicroscopy may help to define grade during URS. There is strong correlation between stage and grade, accordingly correct grading is crucial. The correlation is more pronounced using the 1999 WHO than the 2004 classification: however, the 1999 system risks greater interobserver variability. Using both systems is advisable. A number of tissue-based molecular markers have been studied. None has proven ready for use in clinical practice.Conclusions: Correct grading and staging of UTUC are mandatory for adequate treatment decisions. Optimal diagnostic workup should include CTU with corticomedullary phase, URS with in situ cytology and biopsies. Both WHO classification systems (1999 and 2004) should be used to decrease risk of undergrading or overtreatment.
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| 4. |
- Heinz, Amadeus, et al.
(författare)
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Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification : Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)
- 2023
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 70:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. Methods: Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. Results: Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p =.17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (+/- 12%) and 31% (+/- 14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (+/- 21%), 20% (+/- 16%), and 13% (+/- 23%, p =.008), respectively. Conclusion: Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.
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| 5. |
- Heinz, Amadeus T., et al.
(författare)
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Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma : Data of the European Soft Tissue Sarcoma Registry SoTiSaR
- 2024
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.Procedure: Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan-Meier estimators and Cox proportional hazard models were used to examine event-free survival (EFS) and overall survival (OS) involving also landmark analyses.Results: In the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018), 211 patients were analyzed. Many patients had fusion-positive alveolar RMS (n = 83; 39%). Median age was 9.4 years [0.1-19.7 years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin-D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O-TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion-negative alveolar RMS (n = 9) had an excellent outcome with a 5-year EFS and OS of 100%, compared to patients with embryonal RMS (49%/62%), PAX7- (22%/47%) and PAX3/FOXO1-positive ARMS (10/13%), respectively (p < .001).Conclusions: Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.
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| 6. |
- Hettmer, Simone, et al.
(författare)
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Genetic testing and surveillance in infantile myofibromatosis : a report from the SIOPE Host Genome Working Group
- 2021
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Ingår i: Familial Cancer. - : Springer. - 1389-9600 .- 1573-7292. ; 20 SI:4, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked toPDGFRBgermline variants. SomaticPDGFRBvariants were also detected in solitary and multifocal IM lesions.PDGFRBvariants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRBgermline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
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| 7. |
- Koscielniak, Ewa, et al.
(författare)
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Extraskeletal Ewing sarcoma in children, adolescents, and young adults. An analysis of three prospective studies of the Cooperative Weichteilsarkomstudiengruppe (CWS)
- 2021
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 68:10
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Tidskriftsartikel (refereegranskat)abstract
- Background We have analyzed the outcome of patients with localized extraskeletal Ewing sarcoma (EES) treated in three consecutive Cooperative Weichteilsarkomstudiengruppe (CWS) soft tissue sarcoma (STS) studies: CWS-91, CWS-96, and CWS-2002P. Methods Patients were treated in CWS-91 with four- (vincristine, dactinomycin, doxorubicin, and ifosfamide [VAIA] or cyclophosphamide [VACA II]) or five-drug (+etoposide [EVAIA]) cycles, in CWS-96 they were randomly assigned to receive VAIA or CEVAIE (+carboplatin and etoposide), and in CWS-2002P with VAIA III plus optional maintenance therapy (MT) with cyclophosphamide and vinblastine. Local therapy consisted of resection and/or radiotherapy (RT). Results Two hundred forty-three patients fulfilled the eligibility criteria. The 5-year event-free survival (EFS) and overall survival (OS) were 63% (95% confidence interval [CI] 57-69) and 73% (95% CI 67-79), respectively. The 5-year EFS by study was 64% (95% CI 54-74) in CWS-91, 57% (95% CI 48-66) in CWS-96, and 79% (95% CI 67-91) in CWS-2002P (n.s.). The 5-year OS was 72% (95% CI 62-82) in CWS-91, 70% (95% CI 61-79) in CWS-96, and 86% (95% CI 76-96) in CWS-2002P (n.s.). In CWS-96, 5-year EFS and OS in the VAIA arm versus the CEVAIE were 65% (95% CI 52-81) versus 55% (95% CI 39-76) log-rank p = .13, and 85% (95% CI 75-96) versus 61% (95% CI 45-82), log-rank p = .09. Conclusion Our analysis provides interesting information on the treatment and specificities of EES, which can be useful for a better understanding of this rare entity and should be considered in the development of future clinical trials for Ewing sarcoma defined as FET-ETS fusion positive tumors.
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| 8. |
- Koscielniak, Ewa, et al.
(författare)
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Long-Term Clinical Outcome and Prognostic Factors of Children and Adolescents with Localized Rhabdomyosarcoma Treated on the CWS-2002P Protocol
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Simple SummaryThe major challenge in pediatric oncology is the optimal adaptation of therapy burden to risk profile, aiming to achieve the best outcome with minimum toxicities. The CWS-2002P study in patients <= 21 years with localized rhabdomyosarcoma was developed with this goal by reducing or intensifying the chemotherapy depending on the risk group. An important additional aim was to investigate the use of low-dose maintenance chemotherapy. The risk stratification system was effective in predicting outcomes in the four risk groups with very good long-term results. Neither the reduction nor the intensification of chemotherapy influenced the outcome in comparison to previous studies showing that further de-escalation of chemotherapy should be investigated. The weighting of risk factors used for therapy stratification needs to be reevaluated. Maintenance therapy seemed to have an impact on prognosis.We report here the results of the prospective, non-randomized, historically controlled CWS-2002P study in patients <= 21 years with localized RMS developed with the aim to improve the long-term outcome by adapting the burden of therapy to risk profile and to investigate the feasibility and relation to the outcome of maintenance therapy (MT) in the high-risk groups. Patients were allocated into low-risk (LR), standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. Chemotherapy consisted of vincristine (VCR) and dactinomycin (ACTO-D) for all patients with the addition of ifosfamide (IFO) in the SR, HR, and VHR and doxorubicin (DOX) in the HR and VHR groups. Low-dose cyclophosphamide and vinblastine maintenance therapy (MT) over 6 months was recommended in the HR and VHR groups. A total of 444 patients have been included in this analysis. With a median follow-up of 9 center dot 6 years (IQR 7 center dot 6-10 center dot 9) for patients alive, the 5-year EFS and OS for the whole group was 73% (95% CI 69-77) and 80% (95% CI 76-84), respectively. The 5-year EFS by risk group was 100% in the LR, 79% (95% CI 72-84) in the SR, 69% (95% CI 63-75) in the HR, and 42% (95% CI 23-61) in the VHR (log-rank p = 0.000). The 5-year EFS was 77% (95% CI 70-84) for 155 patients in the HR group who received MT as compared to 63% (95% CI 50-76) for 49 patients who did not (log-rank p = 0.015). Neither the reduction in the IFO dose in the SR nor the increased dose intensity of DOX in HR groups influenced the outcome when compared to the previous CWS and other European studies. MT was feasible, seemed to have an impact on prognosis, and should be studied in a well-controlled prospective trial in this patient population. The weighting of risk factors used for therapy stratification needs to be reevaluated.
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| 9. |
- Koscielniak, Ewa, et al.
(författare)
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Which Patients With Rhabdomyosarcoma Need Radiotherapy? : Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry
- 2023
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Ingår i: Journal of Clinical Oncology. - : Lippincott Williams & Wilkins. - 0732-183X .- 1527-7755. ; 41:31, s. 4916-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSETo analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS).METHODSOne thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5).RESULTSThe 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT.CONCLUSIONRT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.
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| 10. |
- Seitz, Arne, et al.
(författare)
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Concept validation study for fuselage wake-filling propulsion integration
- 2018
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Ingår i: 31st Congress of the International Council of the Aeronautical Sciences, ICAS 2018.
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Konferensbidrag (refereegranskat)abstract
- The present paper provides an overview together with intermediate results of the work-in-progress research performed in the EC-funded Horizon 2020 collaborative project CENTRELINE (“ConcEpt validatioN sTudy foR fusElage wake-filLIng propulsioN integration”), aiming at demonstrating the proof of concept for a groundbreaking approach to synergistic propulsion-airframe integration, the so-called Propulsive Fuselage Concept (PFC). The concept features a turbo-electrically driven propulsive device integrated in the very aft-section of the fuselage, dedicated to the purpose of fuselage wake-filling. Currently at TRL 1-2, CENTRELINE's target is to mature the technological key features of the PFC to TRL 3-4. The core of the targeted proof-of-concept is formed by two experimental test campaigns supported by high-fidelity 3D numerical simulation and integrated multidisciplinary design optimisation techniques for aerodynamics, aero-structures as well as the energy and propulsion system.
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