Erarbeitet von der Sektion 'Narrative psychischer Krisen' im Rahmen des XV. Kongresses der Internationalen Vereinigung für Germanistik (IVG), Graz, Juli 2025 ; Literaturangaben
Access to care; Institutional variability; Metastatic disease; Molecular testing; Non-small cell lung cancer (NSCLC); Practice patterns; Precision oncology; Real-world data
Background - Molecular testing in NSCLC is essential for treatment selection, yet routine implementation remains inconsistent across institutions. Clinical evidence suggests that variability in testing may not be explained by patient or tumor characteristics but might be driven by institutional factors, potentially leading to adverse outcomes. We examined the extent to which variability in AGA testing is attributable to the treating institution. - Methods - We analyzed 6437 adults with stage IIIB/C or IV NSCLC enrolled in the prospective German real-world registry CRISP (2016-2022). Logistic mixed-effects models with AGA testing as the primary outcome were used to determine institutional variability across 171 institutions. Models included patient, tumor, and treatment-related fixed effects with institutions as random effects. Intraclass correlations (ICC) quantified institutional variability unexplained by other covariates. Institution type was tested in secondary analysis, and overall survival in exploratory analysis. - Findings - AGA testing was performed in 77.9% of patients (n=5016). Predicted probabilities for testing use ranged from 30.5% to 93.2% across institutions. Institutions significantly influenced testing use (p<0.001), accounting for 21.4% of the total variance. Variability significantly differed by institution type and was more pronounced in subgroups, e.g., squamous histology (ICC 29.5%) and KRAS testing (ICC 34.4%). Absence of AGA testing was independently associated with inferior survival (HRadj 1.11, 95% CI 1.01-1.23, p=0.029). - Interpretation - Substantial institutional variability exists in AGA testing for NSCLC, which was unexplained by patient or tumor characteristics. This objective evaluation of institution-based variability in testing may emphasize the importance of practice patterns on patient care and may therefore provide an avenue for change.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 236(2026), Artikel-ID 116265, Seite 1-8
von Axel Heep ; E. Binder ; Arne Bischoff ; Lena Dübbel ; L. Wienhausen ; Michael Feldhaus ; F. Heep ; Andrea Hildebrandt ; Tanja Jungmann ; Eduard Malik ; Martin H. Maurer ; Peter Sörös ; Anne Hilgendorff
von Gregor Dombrowsky ; Liselot van der Laan ; Ananília Silva ; Jeroen Breckpot ; Enrique Audain ; Anna Wilsdon ; Michael A. Levy ; Niels Vos ; Marcel Mannens ; Jiao Wang ; Anjali Jain ; Robert Lesurf ; David Winlaw ; Connie R. Bezzina ; Mary Ann Thomas ; Almuth Caliebe ; Sabine Klaassen ; Felix Berger ; Sven Dittrich ; Brigitte Stiller ; Hashim Abdul-Khaliq ; Ingo Dähnert ; Frances Bu’Lock ; Siobhan Loughna ; J. David Brook ; Seema Mital ; Robert B. Russell ; Thomas Pickardt ; Ulrike Bauer ; Hans-Heiner Kramer ; Anselm Uebing ; Peter Henneman ; Bekim Sadikovic ; Alex Postma ; Marc-Phillip Hitz
Veröffentlicht: 07. Januar 2026 ; Gesehen am 16.03.2026
Congenital heart defects; Disulfide-bridges; DNA-methylation; Episignatures; NOTCH1; Tetralogy of Fallot
Background: Congenital heart defects (CHDs) are the most common malformation amongst newborns, with a prevalence of approximately 0.8–2%. The etiology of CHD is highly complex and can be linked to genetic and nongenetic factors. The molecular basis remains partially unclear, and only a minority of patients can be assigned to clear monogenic causes. Methods: Here we analyzed a cohort of 3907 CHD cases and population-matched controls using exome sequencing. In addition, we employed epigenetic profiling on a subset of cases that harbored rare NOTCH1 variants. Results: We identified 24 pathogenic or likely pathogenic single nucleotide variants (SNVs) in NOTCH1 in our exome cohort, as well as a further 15 variants of uncertain significance (VUS) likely to have a deleterious effect. Although the cardiac phenotypes showed some heterogeneity, non-syndromic Tetralogy of Fallot (ToF) and related malformations were the most frequent finding in 56% (22/39). In particular, missense variants altering cysteine residues involved in forming disulfide bridges were identified, specifically in TOF patients. Altogether, NOTCH1-haploinsufficiency represented the most common monogenic cause in our cohort and accounted for an estimated 1% of CHD cases. Combined with additional cases assembled through collaborations, we present 67 individuals with ultrarare variants affecting NOTCH1. This prominent role of NOTCH1 calls for an accurate and accessible evaluation of variants. To this end we explored DNA methylation testing and successfully established a NOTCH1-specific episignature. This signature also displays a robust specificity in relation to 99 other episignatures. Taken together, we found that truncating, splice-altering, as well as missense NOTCH1 variants, can generate a distinct DNAm episignature. Conclusions: We identified that NOTCH1-haploinsufficiency variants represented the most common monogenic cause in our cohort and accounted for an estimated 1 % of CHD cases. Furthermore, we conclude that methylation profiling can contribute to (NOTCH1) variant interpretation and improve the diagnostic management of CHD patients. Lastly, we established a NOTCH1-specific episignature, which represents the first non-syndromic signature, significantly extending the scope of patients that can benefit from methylation analysis.
Genome medicine London : BioMed Central, 2009 18(2026), Artikel-ID 2, Seite 1-21 Online-Ressource
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