von Frank Griesinger ; Maurice Pérol ; Nicolas Girard ; Isabelle Durand-Zaleski ; Stefan Zacharias ; Lise Bosquet ; Martina Jänicke ; Xavier Quantin ; Annika Groth ; Annette Fleitz ; Alan Calleja ; Sonya Patel ; Laure Lacoin ; Melinda J. Daumont ; John R. Penrod ; Robert Carroll ; Daniela Waldenberger ; Dorothée Reynaud ; Michael Thomas ; Christos Chouaid
Objectives - To describe the impact of immune checkpoint inhibitors (ICIs) on treatment patterns and survival outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) in France and Germany. - Materials and Methods - Patients with aNSCLC without known ALK or EGFR mutations receiving first-line (1L) therapy were included from (i) the retrospective Epidemiological-Strategy and Medical Economics Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2018) and (ii) the prospective Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients platform (CRISP, Germany; 2016-2018). Analyses were stratified according to histology. Survival outcomes were estimated using Kaplan-Meier methodology and stratified by year of 1L therapy. Data sources were analysed separately. - Results - In ESME-AMLC and CRISP, 8,046 and 2,359 patients were included in the study, respectively. In both countries, approximately 20 % of all patients received pembrolizumab monotherapy as 1L treatment in 2018. In ESME-AMLC, the proportion receiving an ICI over the course of treatment (any line) increased from 42.2 % (2015) to 56.1 % (2018) in patients with squamous histology, and 28.9 % to 51.9 % with non-squamous/other; in CRISP, it increased from 50.6 % (2016) to 65.2 % (2018) with squamous histology, and 40.8 % to 62.7 % with non-squamous/other. Two-year overall survival from 1L initiation was 36.8 % and 25.6 % in the squamous cohorts and 36.5 % and 30.8 % in the non-squamous/other cohorts in ESME-AMLC and CRISP, respectively. No significant change in overall survival was observed over time; however, the follow-up time available was limited in the later years of the analysis. - Conclusion - The results of this joint research from two large clinical databases in France and Germany demonstrate the growing use of ICIs in the management of aNSCLC. Future analyses will allow for the evaluation of the impact of ICIs on long-term survival of patients with aNSCLC.
Lung cancer Amsterdam [u.a.] : Elsevier, 1985 172(2022) vom: Okt., Seite 65-74 Online-Ressource
von Hamsa Ahmed ; Mohamed Elshabasi ; Marco A. González ; Michael Richter ; Marko Stölzel ; Alfons Weber ; Stephan John Heise ; Thomas Dalibor ; Sascha Schäfer ; Jürgen Parisi
von Sandra Díaz ; Jens Kattge ; Johannes H. C. Cornelissen ; Ian J. Wright ; Sandra Lavorel ; Stéphane Dray ; Björn Reu ; Michael Kleyer ; Vanessa Minden ; Gerhard Zotz
von Hamsa Ahmed ; Mohamed Elshabasi ; Jörg Ohland ; Marko Stölzel ; Alfons Weber ; Robert W. Lechner ; Thomas Dalibor ; Jürgen Parisi ; Sascha Schäfer ; Stephan John Heise
von Hamsa Ahmed ; Vita Solovyeva ; Marco A. González ; Mohamed Elshabasi ; Michael Richter ; Devendra Pareek ; Stephan John Heise ; Marko Stölzel ; Alfons Weber ; Thomas Dalibor ; Sascha Schäfer ; Jürgen Parisi
von Elodie M. Richard ; Somayeh Bakhtiari ; Ashley P. L. Marsh ; Rauan Kaiyrzhanov ; Matias Wagner ; Sheetal Shetty ; Alex Pagnozzi ; Sandra M. Nordlie ; Brandon S. Guida ; Patricia Cornejo ; Helen Magee ; James Liu ; Bethany Y. Norton ; Richard I. Webster ; Lisa Worgan ; Hakon Hakonarson ; Jiankang Li ; Yiran Guo ; Mahim Jain ; Alyssa Blesson ; Lance H. Rodan ; Mary-Alice Abbott ; Anne Comi ; Julie S. Cohen ; Bader Alhaddad ; Thomas Meitinger ; Dominic Lenz ; Andreas Ziegler ; Urania Kotzaeridou ; Theresa Brunet ; Anna Chassevent ; Constance Smith-Hicks ; Joseph Ekstein ; Tzvi Weiden ; Andreas Hahn ; Nazira Zharkinbekova ; Peter Turnpenny ; Arianna Tucci ; Melissa Yelton ; Rita Horvath ; Serdal Gungor ; Semra Hiz ; Yavuz Oktay ; Hanns Lochmuller ; Marcella Zollino ; Manuela Morleo ; Giuseppe Marangi ; Vincenzo Nigro ; Annalaura Torella ; Michele Pinelli ; Simona Amenta ; Ralf A. Husain ; Benita Grossmann ; Marion Rapp ; Claudia Steen ; Iris Marquardt ; Mona Grimmel ; Ute Grasshoff ; Christoph Korenke ; Marta Owczarek-Lipska ; John Neidhardt ; Francesca Clementina Radio ; Cecilia Mancini ; Dianela Judith Claps Sepulveda ; Kirsty McWalter ; Amber Begtrup ; Amy Crunk ; Maria J. Guillen Sacoto ; Richard Person ; Rhonda E. Schnur ; Maria Margherita Mancardi ; Florian Kreuder ; Pasquale Striano ; Federico Zara ; Wendy K. Chung ; Warren A. Marks ; Clare L. van Eyk ; Dani L. Webber ; Mark A. Corbett ; Kelly Harper ; Jesia G. Berry ; Alastair H. MacLennan ; Jozef Gecz ; Marco Tartaglia ; Vincenzo Salpietro ; John Christodoulou ; Jan Kaslin ; Sergio Padilla-Lopez ; Kaya Bilguvar ; Alexander Munchau ; Zubair M. Ahmed ; Robert B. Hufnagel ; Michael C. Fahey ; Reza Maroofian ; Henry Houlden ; Heinrich Sticht ; Shrikant M. Mane ; Aboulfazl Rad ; Barbara Vona ; Sheng Chih Jin ; Tobias B. Haack ; Christine Makowski ; Yoel Hirsch ; Saima Riazuddin ; Michael C. Kruer
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
The American journal of human genetics New York, NY [u.a.] : Cell Press, 1949 108(2021), 10, Seite 2006-2016
von Nasim Parsa ; Jose M. Nieto ; Patrick Powers ; Shuji Mitsuhashi ; Abdelhai Abdelqader ; George Hadzinakos ; Andrea A. Anderloni ; Alessandro Fugazza ; Theodore W. James ; Alexander Arlt ; Mark Ellrichmann ; Jose Ramon Apariacio ; Arvind J. Trindade ; Tyler K. Sevens ; Prabhleen Chahal ; Shawn L. Shah ; Ahmed A. Messallam ; Gabriel Lang ; Phillip Fejleh ; Petros C. Benias ; Divyesh V. Sejpal ; Jason Jones ; Fahad Faisal Mir ; Mohamad Aghaie Meybodi ; Yervant Ichkanian ; Kia Vosoughi ; Aleksey A. Novikov ; Shayan S. Irani ; Rishi Pawa ; Ali M. Ahmed ; Alireza Sedarat ; William Hsueh ; Jochen Hampe ; Reem Z. Sharaiha ; Tyler M. Berzin ; Field F. Willingham ; Vladimir M. Kushnir ; Olaya I Brewer Gutierrez ; Saowanee Ngamruengphong ; Matthew T. Huggett ; Todd H. Baron ; Alessandro Repici ; Douglas G. Adler ; John T. Nasr ; Thomas E. Kowalski ; Vivek Kumbhari ; Vikesh K. Singh ; Mouen A. Khashab
von Mark Zindorf ; Darci Rush ; John Jaeger ; Alan Mix ; Michelle L. Penkrot ; Bernhard Schnetger ; Frances R. Sidgwick ; Helen M. Talbot ; Cees van der Land ; Thomas Wagner ; Maureen Walczak ; Christian März
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