Available online: 2 October 2019 ; Gesehen am 08.07.2020
penumbra; photon
For any detector to be used for the determination of absorbed dose at the point of measurement in water a basic equation is required to convert the reading of the detector into absorbed dose in water. The German DIN 6800 part 1 provides a general formalism for that. A further differentiated formalism applicable to photon dosimetry is suggested in this work. This modified formalism presents the two following still general and at the same time fundamental properties of any dosimetry detector: a) a clear distinction of correction factors with respect to the physical processes involved during the measurement, and b) the fact that the process of energy absorption in the detector is determined by the spectral distribution of the fluence of the secondary charged particles. It is concluded that based on the modified formalism and knowing this spectral distribution within the detector a general method is available with benefits for ionization chambers as well as for any other dosimetry detector and which is applicable at reference as well as non-reference conditions without any preconditions.
Zeitschrift für medizinische Physik Amsterdam [u.a.] : Elsevier, 1990 30(2020), 1, Seite 24-39
von Insa Seeger ; Andreas Klausen ; Stefan Thate ; Frank Flake ; Oliver Peters ; Walter Rempe ; Michael Peter ; Frank Scheinichen ; Ulf Günther ; Rainer Röhrig ; Andreas Weyland
von Petros Christopoulos ; Martina Kirchner ; Farastuk Bozorgmehr ; Nikolaus Magios ; Daniel Kazdal ; Anna-Lena Volckmar ; Lena Marie Brückner ; Tilmann Bochtler ; Mark Kriegsmann ; Volker Endris ; Roland Penzel ; Katharina Kriegsmann ; Martin E. Eichhorn ; Felix Herth ; Claus Peter Heußel ; Rami El-Shafie ; Marc Schneider ; Thomas Muley ; Michael Meister ; Peter Schirmacher ; Helge Bischoff ; Frank Griesinger ; Albrecht Stenzinger ; Michael Thomas
Objective - Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. - Materials and methods - To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). - Results - EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+ NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. - Conclusions - EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.
Lung cancer Amsterdam [u.a.] : Elsevier, 1985 148(2020), Seite 105-112 Online-Ressource
Published Online October 9, 2019 ; Gesehen am 15.04.2020
Background - Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. - Methods - We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m2 treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0·8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m2 intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1·3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393). - Findings - Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15·4 months (IQR 8·8-23·6) for patients treated with treosulfan and 17·4 months (6·3-23·4) for those treated with busulfan. 2-year event-free survival was 64·0% (95% CI 56·0-70·9) in the treosulfan group and 50·4% (42·8-57·5) in the busulfan group (HR 0·65 [95% CI 0·47-0·90]; p<0·0001 for non-inferiority, p=0·0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related. - Interpretation - Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population. - Funding - medac GmbH.
The lancet. Haematology London [u.a.] : Elsevier, 2014 7(2020), 1, Seite e28-e39 Online-Ressource
von Matthew A. Charette ; Lauren E. Kipp ; Laramie T. Jensen ; Jessica S. Dabrowski ; Laura M. Whitmore ; Jessica N. Fitzsimmons ; Tatiana Williford ; Adam Ulfsbo ; Elizabeth Jones ; Randelle M. Bundy ; Sebastian M. Vivancos ; Katharina Pahnke ; Ronja Paffrath
von Andreas Mock ; Christoph E. Heilig ; Simon Kreutzfeldt ; Daniel Hübschmann ; Christoph Heining ; Evelin Schrök ; Benedikt Brors ; Albrecht Stenzinger ; Dirk Jäger ; Richard Friedrich Schlenk ; Hanno Glimm ; Stefan Fröhling ; Peter Horak ; Frank Griesinger
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