This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB-C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016-2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5-3.2) in squamous and 2.5 months (2.3-2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4-3.1) and 2.3 months (2.0-2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.
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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