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Abstract Background In the pivotal phase III RECOURSE trial, trifluridine/tipiracil (FTD/TPI) improved progression-free and overall survival (PFS, OS) of patients with pre-treated metastatic colorectal cancer (mCRC). Subsequently, the TALLISUR trial provided post-authorisation efficacy and safety data and patient-reported outcomes on quality of life (QoL) in a German patient cohort. The present analysis reports the final data on efficacy, safety and QoL and investigates the impact of baseline characteristics and associated prognostic subgroups on outcome. Methods In this prospective, multi-centre, Germany-wide, phase IV study, patients with pre-treated mCRC were given the choice to receive either FTD/TPI or best supportive care (BSC). To assess the primary endpoint, QoL, EORTC QLQ-C30 questionnaires were employed. Secondary endpoints included QoL assessed through EQ-5D-5L questionnaires, OS, PFS and safety. Additionally, 3 subgroups were defined according to a post-hoc analysis of the RECOURSE trial: best, good and poor prognostic characteristics (BPC, GPC, PPC). Patients with

Abstract Background Currently, a conclusive experience on the uniform implementation and benefits of day hospice structures and interventions is lacking in Germany. The following questions should be clarified: (1) Which structural conditions and interventional measures should be established in day hospices from the point of view of patients, relatives, and specialist staff?; (2) Are the planned structures or interventions feasible and implementable under real conditions and accepted by patients, relatives, and staff?; (3) How can a final implementation and intervention catalog for day hospices be designed?; (4) Is this final catalog of services feasible, reasonable, economical, and effective under everyday conditions in day hospices? Methods We planned to perform a multistage investigation, guided by the Medical Research Council Framework for the development and evaluation of complex interventions. In Stage 1, an initial theoretical construct on structures and interventions will be established through an extensive literature and guideline review on day hospices and through qualitative interviews. In a nominal group process, we will create a catalog of offers. In Stage 2, feasibility testing is conducted in a single-day hospice under real-life conditions using quantitative quality indicators and qualitative interviews. Structures and interventions can be adapted here if necessary. In a second nominal group process, a final structure and offer catalog is created, which is then implemented in Stage 3 in the day hospice under investigation and evaluated under real daily conditions through a process and effectiveness test. For this purpose, qualitative and quantitative quality indicators will be used and a comparative cohort of patients who are not cared for in the day hospice – but in the same network structure (oncology–palliative care network Lower Bavaria) – is examined. Discussion Finally, the initial statements on the reasonable and realizable structures or interventions in day hospices and their benefits in daily real-life conditions as well as possible optimization processes shall be made. Trial registration The study was retrospectively registered in the German Clinical Trials Register (DRKS-ID DRKS00031613, registration date April 04, 2023) and the display portal of the Center for Clinical Trials of the University Hospital Regensburg (Z-2022-1734-6, registration date July 01, 2023).

In newly diagnosed acute myeloid leukemia, immediate initiation of treatment is standard of care. However, deferral of antileukemic therapy may be indicated to assess comorbidities or pre-therapeutic risk factors. We explored the impact of time from diagnosis to treatment on outcomes in newly diagnosed acute myeloid leukemia undergoing venetoclax-based therapy in two distinct cohorts. By querying the Study Alliance Leukemia database and the global health network TriNetX, we identified 138 and 717 patients respectively with an average age of 76 and 72 years who received venetoclax-based firstline therapy. When comparing patients who started treatment earlier or later than 10 days after initial diagnosis, no significant difference in median overall survival was observed - neither in the SAL cohort (7.7 vs. 9.6 months, p=.42) nor in the TriNetX cohort (7.5 vs. 7.2 months, p=.41). Similarly, severe infections, bleeding, and thromboembolic events were equally observed between early and later treatments, both in the overall patient groups and specific subgroups (age ≥75 years or leukocytes ≥20x109/L). This retrospective analysis indicates that delaying the start of venetoclax-based therapy in newly diagnosed acute myeloid leukemia might be a safe option for selected patients, provided that close clinical monitoring is performed.

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients. Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042). Results: Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), p equals 0.004. Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Abstract Tandem-duplication mutations of the UBTF gene (UBTF-TDs) coding for the upstream binding transcription factor have recently been described in pediatric patients with acute myeloid leukemia (AML) and were found to be associated with particular genetics (trisomy 8 (+8), FLT3-internal tandem duplications (FLT3-ITD), WT1-mutations) and inferior outcome. Due to limited knowledge on UBTF-TDs in adult AML, we screened 4247 newly diagnosed adult AML and higher-risk myelodysplastic syndrome (MDS) patients using high-resolution fragment analysis. UBTF-TDs were overall rare (n = 52/4247; 1.2%), but significantly enriched in younger patients (median age 41 years) and associated with MDS-related morphology as well as significantly lower hemoglobin and platelet levels. Patients with UBTF-TDs had significantly higher rates of +8 (34% vs. 9%), WT1 (52% vs. 7%) and FLT3-ITD (50% vs. 20.8%) co-mutations, whereas UBTF-TDs were mutually exclusive with several class-defining lesions such as mutant NPM1, in-frame CEBPA bZIP mutations as well as t(8;21). Based on the high-variant allele frequency found and the fact that all relapsed patients analyzed (n = 5) retained the UBTF-TD mutation, UBTF-TDs represent early clonal events and are stable over the disease course. In univariate analysis, UBTF-TDs did not represent a significant factor for overall or relapse-free survival in the entire cohort. However, in patients under 50 years of age, who represent the majority of UBTF-mutant patients, UBTF-TDs were an independent prognostic factor for inferior event-free (EFS), relapse-free (RFS) and overall survival (OS), which was confirmed by multivariable analyses including established risk factors such as age and ELN2022 genetic risk groups (EFS [HR: 2.20; 95% CI 1.52–3.17, p

Abstract Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.

Background: More than 80% of the residents in German hospices suffer from tumor disease. But the administration of supportive-oncological therapies in hospices for symptom control is controversially discussed. Objectives: This study aims to investigate the care situation of tumor patients in German hospices with regard to medical care and the use of supportive-oncological therapies. Methods: In February 2019, all hospices in Germany were offered the opportunity to participate in an anonymous online survey on medical and drug care for their tumor patients. The survey was conducted using the online platform SoSci Survey and ended in April 2019. The analysis was descriptive. Results: Of 202 hospices, 112 responded to the questionnaire. The hospices were distributed nationwide. Most have 8 to 10 places. More than 80% of hospice residents are tumor patients, and the length of stay is usually three to four weeks. Medical care is primarily provided by primary care physicians. While specialized outpatient palliative care is increasingly involved in care, hematologists/oncologists are rarely represented. Supportive-oncological therapies are rarely prescribed, whereas medication for other chronic conditions is often continued. The percentage of supportive-oncological therapies prescribed is higher in hospices with oncology co-care. Conclusions: Although most hospice residents suffer from malignant disease, co-care by a hematologist/oncologist is rare. Supportive-oncology therapies, particularly for symptom relief, may therefore be rarely used. However, since a small select group of hospice residents may benefit from these therapies, further investigation in this direction should be undertaken.

Abstract Background Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. Methods We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. Results AML patients with EM presented with significantly higher counts of white blood cells (p

Abstract Background Colon cancer (CC) is a disease of elderly patients (pts.) with a median age of 73 years (yrs.). Lack of data about the effects of adjuvant chemotherapy (ACT) is caused by underrepresentation of this clinically relevant cohort in interventional trials. We analyzed real‐world data from the German CPP registry with regard to a possible benefit of ACT in elderly (70+ yrs.) versus younger pts. (50 to

Abstract To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (

Abstract Background Infection with SARS‐CoV‐2 leads to COVID‐19, the course of which is highly variable and depends on numerous patient‐specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID‐19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID‐19 in patients with cancer is of great importance. Methods Patients diagnosed with solid tumors or hematological malignancies and PCR‐confirmed SARS‐CoV‐2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients’ cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS‐CoV‐2 infection was graded according to the WHO. Results A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS‐CoV‐2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID‐19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS‐CoV‐2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID‐19‐related death. Conclusion The course of COVID‐19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID‐19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.

Abstract Background There is controversy regarding the practical implementation of symptom-focused oncological cancer therapies to hospice residents. In this study, we aim to analyse the use and indication of supportive-oncological cancer therapies in hospices. Methods We conducted a retrospective survey of all residents of two hospice centres in the government district of Lower Bavaria, Germany. Hospice 1 (H1) was a member of an oncological–palliative medical network, and hospice 2 (H2) was independently organized. The evaluation period was the first 40 months after the opening of the respective hospice care centre. Demographical and epidemiological data as well as indications and type of supportive-oncological cancer therapies were recorded. A descriptive analysis and statistical tests were performed. Results Of the 706 residents, 645 had an underlying malignant disease. The average age was 72 years and the mean residence time was 28 days. The most frequent cancer types were gastrointestinal cancers, gynaecological cancers and bronchial carcinomas. Overall 39 residents (33 in H1 and 6 in H2, p

IntroductionThe Covid-19 pandemic has caused great personal stress for medical staff. To ensure adequate outpatient care for cancer patients, extensive safety and hygiene measures must be taken. This interview-based study examines the effects-both personal and professional-of the pandemic on the work routine of outpatient hematology/oncology nurses and medical assistants.Patients, materials and methodsHalf a year after the outbreak of Covid-19 and the introduction of infection control regulations in three outpatient hematological/oncological centers, the affected medical staff (n = 15) were surveyed about the consequences for patient care and clinical work using audio-recorded telephone interviews. The interviews were transcribed and analyzed using a qualitative content analysis.ResultsThe Covid-19 pandemic has complicated the medical care of cancer patients, but only a slight deterioration of medical and psycho-oncological care was observed. The level of stress experienced by medical staff is moderate, with hygiene and safety measures at the workplace helping to reduce stress.ConclusionFrom the point of view of medical staff, the Covid-19 pandemic has had a moderate impact on the outpatient care of cancer patients. Safety measures against Covid-19 are decisive for ensuring the continuation of therapy and for motivating employees.

Introduction Five months after COVID-19 first occurred and protective regulations were introduced, patients at three outpatient hematological/oncological centers in Bavaria who had received antiproliferative tumor therapy (n = 30) were questioned about the pandemic’s impact. Patients, materials and methods In recorded semi-structured telephone interviews, the patients answered questions about their quality of life, treatment procedures, their relationship with medical care staff and modern communication technologies. Each interview consisted of 28 questions. The average length of an interview was 30 minutes. The interviews were transcribed and analyzed by means of a qualitative content analysis according to Mayring. Results The COVID-19 pandemic adds to the burden of patients by decreasing their social contacts. They perceived the new isolation and protective measures in outpatient clinics as mostly positive and said its impact had been only slightly adverse. With the implemented safety measures, they feel adequately protected and looked after and want their antiproliferative therapy to be performed as scheduled. Talking to medical staff provides additional reassurance. Conclusion Although the COVID-19 pandemic has exacerbated the social isolation of tumor patients, it has had only a minor effect on tumor therapy in the surveyed patient population. The benefits of modern communication options to tumor patients remains uncertain and should be investigated further in future studies.

Der Beitrag setzt sich kritisch mit einem derzeit häufig rezipierten Verständnis des Begriffs ›Formfunktion‹ (formal function) auseinander, das im Anschluss u.a. an die Formenlehre von Erwin Ratz im nordamerikanischen Diskurs entwickelt wurde. Ausgehend von dieser Kritik legt der Beitrag anhand der Formfunktionen ›Hauptsatz‹ (main theme), ›Überleitung‹ (transition), ›Seitensatz‹ (subordinate theme) und ›Schlussgruppe‹ (closing section) eine alternative Auffassung für die musikalische Analyse von Sonatenhauptsätzen dar, die an Sonatenkompositionen aus der zweiten Hälfte des 18. sowie des frühen 19. Jahrhunderts veranschaulicht wird. // This essay offers a critical view of a frequently adopted understanding of the term ›formal function‹, which had been established in North America in response to the theories of Erwin Ratz. Applying this critical view to the formal functions ›main theme‹, ›transition‹, ›subordinate theme‹, and ›closing section‹, an alternative concept for the musical analysis of sonata form is developed and illustrated with compositions from the second half of the eighteenth century and the early nineteenth century.

In dem folgenden Beitrag wird vom ›Satzmodell‹ (›Satztypen und -formeln‹ im Sinne von Carl Dahlhaus) ausgehend ein Modellbegriff entwickelt, der die Anforderungen empirischer Forschung im Bereich der musikalischen Analyse erfüllt. In einem ersten Schritt werden hierzu die Möglichkeiten und Grenzen des Begriffs ›Satzmodell‹ erörtert. In einem zweiten Schritt wird gezeigt, dass sich die Eigenschaft Formfunktion nicht über Satzmodelle, sondern nur über weitere Modelle (Metamodelle), beschreiben lässt, wie z.B. die in verschiedenen Diskursen (Schenkerian Analysis, Partimento) verwendete Tonleiterstruktur. Abschließend werden ausgewählte Modelle mithilfe der Unified Modelling Language (UML) skizziert und der Wert des Modelldesigns für eine wissenschaftliche Forschung im Sinne Niklas Luhmanns aufgezeigt. Taking the idea of the ›Satzmodell‹ (compositional types and formulas as defined by Carl Dahlhaus) the following article develops a concept of musical models which meets the demands of empirical research in the field of musical analysis. In a first step, the possibilities and limitations of the concept of the ›Satzmodell‹ will be discussed. In a second step, it will be shown that the property of formal function cannot be described in terms of schema theory, but requires further models (metamodels), such as scale structure, as used in various discourses (Schenkerian Analysis, Partimento). Finally, selected models will be outlined using the Unified Modelling Language (UML) and the value of model design for scientific research in the sense of Niklas Luhmann will be demonstrated.

Flow cytometry (FC) facilitates diagnosis of peripheral T-cell non-Hodgkin lymphoma (T-NHL), but overlapping features between reactive and neoplastic T-cell proliferations often hamper a rapid assessment. One hundred forty peripheral blood samples submitted to diagnostic FC for T-cell immunophenotyping were retrospectively analyzed. A T-cell population with a conspicuous aberrant surface epitope expression pattern was observed in 18 cases and diagnostic follow up was performed. The aberrant T-cell population exhibited a low scatter profile, a CD7-negative/low, CD8-low and CD3-positive immunophenotype, and monoclonal T-cell receptor expansion. T-NHL was ruled out by follow up in all cases. Epstein-Barr virus infection was diagnosed in 12 cases, cytomegalovirus infection in three cases; one patient had been vaccinated. The irregular subpopulation disappeared spontaneously within days or weeks. We describe a novel peripheral blood T-cell subpopulation with a low light scatter and CD8-low, CD7-negative/low and CD3-positive marker expression profile, which indicates reactive T-cell expansion in patients who present with peripheral lymphadenopathy and/or B symptoms.

Nach einer methodisch orientierten Analyse von drei Lehrproben erfolgen Überlegungen zur Didaktik des Musiktheorieunterrichts sowie zum Methodikunterricht des Hauptfachs Musiktheorie. Diese Überlegungen nehmen Bezug auf aktuelle Themen des erziehungswissenschaftlichen Diskurses. Dazu gehören das viel diskutierte Thema ›Kompetenzorientierung‹, die von Niklas Luhmann aufgezeigte Trivialisierungsproblematik und die derzeit wesentlich von John Hattie beeinflusste Diskussion zur Selbstevaluation Lehrender. Vor diesem Hintergrund wird ein kritisches Schlaglicht auf die gegenwärtige Praxis von Bewerbungsverfahren in der akademischen Musiktheorie geworfen. A methodically oriented analysis of three demonstration lessons is followed by contemplations on didactics of music theory and the challenge of giving methodological instructions to music theory students. These contemplations refer to topics currently being discussed in the discourse on educational science, among them the much respected subject of ‘Kompetenzorientierung’, the problem of ‘Trivialisierung’ as demonstrated by Niklas Luhmann and the debate on self-evaluation of teachers, which is currently substantially influenced by John Hattie. Against this backdrop a critical light is cast on the current practice of application procedures in academic music theory.

Eine differenzierte Formanalyse der seit 1950 entstandenen Pop-/Rockmusik ist möglich, wenn die englischsprachigen Begriffe ›Verse‹, ›Chorus‹, ›Headline‹, ›Intro‹, ›Outro‹, ›Bridge‹, ›Instrumental Solo‹, ›Interlude‹, ›Prechorus‹ und ›Transitional Bridge‹ für die Beschreibung von Musik reserviert werden, die deutschen Begriffe ›Strophe‹, ›Refrain‹ und ›Refrainzeile‹ hingegen der ausschließlichen Beschreibung eines Textes dienen. In dem folgenden Beitrag werden Probleme bezüglich der herkömmlichen Verwendung der Termini aufgezeigt und Vor- wie Nachteile einer terminologischen Differenzierung erörtert. Die Exemplifizierung der Fachbegriffe erfolgt an den Standard-Formmodellen ›Verse-Form‹, ›Verse-Bridge-Form‹, ›Verse-Chorus-Form‹ und ›Verse-Chorus-Bridge-Form‹.

Im Hinblick auf eine Theorie der Sonatenhauptsatzform gehört die nähere Bestimmung des Formteils ›Überleitung‹ zu den Desideraten der Forschung. Der folgende Beitrag zeigt den Versuch, vor dem Hintergrund zahlreicher Analysen und unter Berücksichtigung zeitgenössischer Quellen belastbare Überleitungsmodelle zu definieren, die wiederum Grundlage für einen umfassenden Theorieaufbau zum Thema ›Überleitung‹ sein könnten. Hinsichtlich der Musik Mozarts ist dieser Beitrag an ein öffentlich zugängliches Datenbankprojekt gekoppelt, das dazu einlädt, noch nicht untersuchte Überleitungen einzugeben und im Bestand der Eingaben zu recherchieren.