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
von Bernhard Wörmann ; Carsten Bokemeyer ; Thomas Burmeister ; Claus-Henning Köhne ; Matthias Schwab ; Dirk Arnold ; Jens-Uwe Blohmer ; Markus Borner ; Sara Brucker ; Ingolf Cascorbi ; Thomas Decker ; Maike de Wit ; Andreas Dietz ; Hermann Einsele ; Wolfgang Eisterer ; Gunnar Folprecht ; Wolfgang Hilbe ; Jürgen Hoffmann ; Wolfgang Knauf ; Volker Kunzmann ; Carlo R. Largiadèr ; Sylvie Lorenzen ; Diana Lüftner ; Markus Moehler ; Markus M. Nöthen ; Christian Pox ; Anke Reinacher-Schick ; Anton Scharl ; Brigitte Schlegelberger ; Thomas Seufferlein ; Marianne Sinn ; Matthias Stroth ; Ingo Tamm ; Lorenz Trümper ; Martin Wilhelm ; Ewald Wöll ; Ralf-Dieter Hofheinz
<b><i>Background:</i></b> 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%. <b><i>Summary:</i></b> Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (<i>DPYD</i>). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. <b><i>Key Messages:</i></b> (i) Patients should be tested for the 4 most common genetic <i>DPYD</i> variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
Oncology research and treatment Basel : Karger, 2014 43(2020), 11, Seite 628-636 Online-Ressource
von Eric Van Cutsem ; Heinz-Josef Lenz ; Claus-Henning Köhne ; Volker Heinemann ; Sabine Tijpar ; Ivan Melezínek ; Frank Beier ; Christopher Stroh ; Philippe Rougier ; J. Han van Krieken ; Fortunato Ciardiello
von Carsten Bokemeyer ; Claus-Henning Köhne ; F. Ciardiello ; Hans-Joachim Lenz ; Volker Heinemann ; U. Klinkhardt ; F. Beier ; K. Dücker ; J. H. Krieken ; S. Tejpar
Aufn.: Music Academy MOD, September 1989. - Enth.: Windfall. Mardi gras. Theme from fantasy / Thomas Brown. [EST: Werke / Ausw.]. Panache / Cees Teeling. Get-Hip / Joachim Sponsel. Changing constellation / Rainer Kolbeck. Suite for solo drum set and percussion / David Mancini. - Interpr.: Sponsel, Joachim [Dir., Versch. Instr.]. Basler, Wolfgang [Parade snare drum]. Beck, Guido [Versch. Instr.]. Engel, Julia [Versch. Instr.]. Faigle, Horst [Versch. Instr.]. Heller, Volker [Versch. Instr.]. Hiltner, Tom [Keyboards, b synthesizer]. Hupp, Thomas [Tablas]. Illing, Heinrich [Versch. Instr.]. Kolbeck, Rainer [el-b]. Mehling, Claus [Versch Instr.]. Pöll, Dieter [Versch. Instr.]. Schay, Daniel [Versch. Instr.]. Schmidt, Florian [Versch. Instr.]. Traumann, Matthias [Versch. Instr.]. Verna, Markus [Versch. Instr.]. Weiß, Chris [Versch. Instr.]. Wickel, Marcus [Versch. Instr.]. Wunderlich, Rolf [Versch. Instr.]. - Best.-Nr. AU 31315