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Institute
Schaudt, André ; Golling, Markus T. ; Schwarz, Wolfram ; Zangos, Stephan ; Kriener, Susanne ; Vogl, Thomas J. ; Bechstein, Wolf Otto
Einleitung: Für die meisten Patienten mit HCC ist die LTX die einzige kurative Behandlungsoption. Bei diesen Patienten scheint eine Kontrolle der Erkrankung durch lokale Verfahren im Intervall bis zur LTX zu erreichen zu sein. Als das beste Verfahren gilt die transarterielle Chemoembolisation (TACE). Die Effektivität ist jedoch umstritten. Möglicherweise kann sie aber Patienten startifizieren, die ein hohes Rezidivrisiko haben.
Material und Methoden: Im Zeitraum zwischen 1995 und 2005 wurden n=27 Patienten mit HCC im Alter zwischen 22 und 69 Jahren transplantiert. Hiervon erhielten n=15 Patienten eine Vorbehandlung in Form einer alleinigen TACE oder kombiniert mit PEI [n=1] bzw. LITT [n=1]. Retrospektiv wurde das Gesamtüberleben sowie das „Event-free-survival“ (Rezidiv, Reinfektion und Tod) analysiert.
Ergebnisse: Die mittlere Wartezeit betrug bei Patienten in der TACE-Gruppe 214 Tage, bei Patienten ohne Vorbehandlung 133 Tage. Bei einem mittleren Nachbeobachtungszeitraum von 1097 ± 1193 Tagen für TACE-Patienten und 1674 ± 966 Tagen für non-TACE-Patienten betrug das Überleben für Patienten, die mit TACE vorbehandelt wurden 83,3%, für Patienten, die keine TACE erhielten 86.7% (p=0,5693). Gleiches fand sich für das Event-free-survival (p=0,8823). Das Gesamtüberleben der Patienten, die auf der Warteliste einen Tumorprogress hatten lag bei 77%, während Patienten mit stabiler Tumorgröße oder Regredienz der Tumore ein Überleben von 93% aufwiesen (p=0,0153). Unter TACE-Behandlung zeigten 5/15 Patienten eine zunehmende Anzahl an Herden im histologischen Präparat verglichen mit der Ausgangsbildgebung. Nur bei einem Patienten zeigte sich der Progress der Erkrankung bereits in der präoperativen Bildgebung. Patienten mit einem Progress der Erkrankung hatten ein Gesamtüberleben von 60%, während Patienten mit „stable disease“ oder Rückgang der Herde ein Gesamtüberleben von 100% hatten (p=0,0180).
Schlussfolgerung: Unseren Ergebnisse zufolge ist der Effekt der TACE als Bridgingverfahren auf das Überleben der Patienten fraglich. Allerdings scheint die TACE zur Riskostratifizierung geeignet zu sein. In unserem Patientenkollektiv hatten Patienten, die eine Progredienz der Erkrankung auf der Warteliste zeigten ein signifikant schlechteres Gesamtüberleben. Dies gilt auch bei ausschließlicher Betrachtung der Patienten mit TACE.
Neumann, Martin ; Coskun, Ebru ; Fransecky, Lars ; Mochmann, Liliana H. ; Bartram, Isabelle ; Sartangi, Nasrin Farhadi ; Heesch, Sandra ; Gökbuget, Nicola ; Schwartz, Stefan ; Brandts, Christian Hubertus ; Schlee, Cornelia ; Haas, Rainer ; Dührsen, Ulrich ; Griesshammer, Martin ; Döhner, Hartmut ; Ehninger, Gerhard ; Burmeister, Thomas ; Blau, Olga ; Thiel, Eckhard ; Hoelzer, Dieter ; Hofmann, Wolf-Karsten ; Baldus, Claudia
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.
Götze, Thorsten ; Batran, Salah-Eddin al- ; Pabst, Urs ; Reymond, Marc ; Tempfer, Clemens ; Bechstein, Wolf Otto ; Bankstahl, Ulli ; Gockel, Ines ; Königsrainer, Alfred ; Kraus, Thomas ; Mönig, Stefan Paul ; Rau, Beate ; Schwarzbach, Matthias ; Piso, Pompiliu
Background: Peritoneal metastasis is a common and dismal evolution of several gastrointestinal (GI) tumors, including gastric, colorectal, hepatobiliary, pancreatic, and other cancers. The therapy of peritoneal metastasis is largely palliative; with the aim of prolonging life and preserving its quality. In the meantime, a significant pharmacological advantage of intraperitoneal chemotherapy was documented in the preclinical model, and numerous clinical studies have delivered promising clinical results.
Methods: This is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy vs. intravenous systemic chemotherapy alone on patients with metastatic upper GI tumors with a peritoneal seeding. Upper GI-adenocarcinomas originated from biliary tract, pancreas and stomach, or esophago- gastric junction are eligible. Patients in the study are treated with standard of care systemic palliative chemotherapy (mFOLFOX6) vs. PIPAC with intravenous (i.v.) chemotherapy (mFOLFOX6). Patients in first line with first diagnosed peritoneal seeding are eligible. Primary outcome is progression free survival (PFS).
Conclusions: PIPAC-procedure is explicit a palliative method but it delivers cytotoxic therapy like in hyperthermic intraperitoneal chemotherapy (HIPEC)-procedure directly to the tumor in a minimally invasive technique, without the need for consideration of the peritoneal-plasma barrier. The technique of PIPAC is minimally invasive and very gentle and the complete procedure takes only round about 45 min and, therefore, optimal in a clearly palliative situation where cure is not the goal. It is also ideal for using this approach in a first line situation, where deepest response should be achieved. The symbiosis of systemic therapy and potentially effective surgery has to be well-planned without deterioration of the patient due to aggressive way of surgery like in cytoreductive surgery (CRS)+HIPEC.
Trial registration: EudraCT: 2018-001035-40.
Schebelle, Laura ; Wolf, Claudia ; Stribl, Carola ; Javaheri, Tahereh ; Schnütgen, Frank ; Ettinger, Andreas ; Ivics, Zoltán ; Hansen, Jens ; Ruiz, Patricia ; Melchner, Harald von ; Wurst, Wolfgang ; Floss, Thomas
Recombinase-mediated cassette exchange (RMCE) exploits the possibility to unidirectionally exchange any genetic material flanked by heterotypic recombinase recognition sites (RRS) with target sites in the genome. Due to a limited number of available pre-fabricated target sites, RMCE in mouse embryonic stem (ES) cells has not been tapped to its full potential to date. Here, we introduce a universal system, which allows the targeted insertion of any given transcriptional unit into 85 742 previously annotated retroviral conditional gene trap insertions, representing 7013 independent genes in mouse ES cells, by RMCE. This system can be used to express any given cDNA under the control of endogenous trapped promoters in vivo, as well as for the generation of transposon ‘launch pads’ for chromosomal region-specific ‘Sleeping Beauty’ insertional mutagenesis. Moreover, transcription of the gene-of-interest is only activated upon Cre-recombinase activity, a feature that adds conditionality to this expression system, which is demonstrated in vivo. The use of the RMCE system presented in this work requires one single-cloning step followed by one overnight gateway clonase reaction and subsequent cassette exchange in ES cells with efficiencies of 40% in average.
Nast, Alexander ; Kopp, Ina ; Augustin, Matthias ; Banditt, Kirstin-Benita ; Boehncke, Wolf-Henning ; Follmann, Markus ; Friedrich, Markus ; Huber, Matthias ; Kahl, Christina ; Klaus, Joachim ; Koza, Joachim ; Kreiselmaier, Inga ; Mohr, Johannes ; Mrowietz, Ulrich ; Ockenfels, Hans-Michael ; Orzechowski, Hans-Dieter ; Prinz, Jörg ; Reich, Kristian ; Rosenbach, Thomas ; Rosumeck, Stefanie ; Schlaeger, Martin ; Schmid-Ott, Gerhard ; Sebastian, Michael ; Streit, Volker ; Weberschock, Tobias Bernd ; Rzany, Berthold
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).
Knauer, Shirley ; Knauer, Shirley K. ; Krämer, Oliver Holger ; Knösel, Thomas ; Engels, Knut ; Rödel, Franz ; Brieger, Jürgen ; Mann, Wolf ; Habtemichael, Negusse ; Petersen, Ivar ; Heinzel, Thorsten ; Stauber, Roland
Survivin functions as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Since survivin is a highly relevant target for tumor therapy, we investigated whether interference with it’s dynamic cellular localization represents a novel strategy to inhibit survivin’s cancer promoting functions. We confirmed survivin overexpression in head and neck as well as in colorectal cancers and identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. Importantly, nuclear export was required for survivin mediated protection against chemo- and radiotherapy-induced apoptosis by securing efficient interference with cytoplasmic caspases. In dividing cells, the NES was required for tethering of survivin and of the survivin/Aurora-B kinase complex to the mitotic machinery, which was inevitable for proper cell division. The clinical relevance of our findings was supported by showing that preferential nuclear localization of survivin correlated with enhanced survival in a cohort of colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We here show that nuclear export is essential for the tumor promoting activities of survivin and encourage the identification of chemical inhibitors to specifically interfere with survivin’s nuclear export as a novel class of anticancer therapeutics.
Younsi, Alexander ; Unterberg, Andreas ; Marzi, Ingo ; Woschek, Mathias ; Lemcke, Johannes ; Maegele, Marc ; Bendella, Habib ; Mauer, Uwe Max ; Scheer, Magnus ; Uhl, Eberhard ; Friedrich, Michaela ; Meixensberger, Jürgen ; Lindner, Dirk ; Westermaier, Thomas L. ; Stetter, Christian E. ; Clusmann, Hans ; Hamou, Hussam Aldin ; Schmieder, Kirsten ; Gierthmühlen, Mortimer ; Steudel, Wolf-Ingo
Objective: Nationwide data on the epidemiology, treatment characteristics, and long-term outcome of severe traumatic brain injury (TBI) in Germany is not yet existing. Neurosurgeons from the German Neurosurgery Society (DGNC) and traumatologists from the German Trauma Society (DGU), therefore, joined forces in 2016 to conceptualize a TBI module for the well-established Trauma Register of the DGU (TR-DGU). Here, we report how this “German National TBI registry (GNTR)” has been developed, implemented, and tested in a recently completed pilot period.
Methods: The conception and implementation process of the GNTR from August 2016 to February 2019 is described, and results of its 23-months long pilot period from February 2019 to December 2020 are presented. For the pilot period, TBI patients were prospectively enrolled at nine neurosurgical and traumatological hospitals across Germany. Inclusion criteria were treatment on the ICU ≥ 24h, or an ISS score ≥ 16. A variety of clinical, imaging, and laboratory parameters were collected, and the GOSE score was used to assess the outcome at discharge and 6- and 12 months follow-up.
Results: Details on the structure and dataset of the GNTR as well as milestones and pitfalls during its conception and implementation, are outlined. During the pilot period, a total of 264 TBI patients were enrolled. Their demographic characteristics, clinical, imaging, and radiological findings, and their early mortality and functional outcome are described. Furthermore, factors associated with an unfavorable outcome (GOSE 1-4) are assessed using uni- and multivariate regression analyses. Finally, problems and future directions of the GNTR are discussed.
Conclusion: The pilot period of the GNTR offers a first glance at the current epidemiology and treatment characteristics of TBI patients in Germany. More importantly, they show how a national TBI registry yielding high-quality prospective data can be developed, implemented, and tested within four years
Obermeier, Martin ; Berg, Thomas ; Sichtig, Nadine ; Braun, Patrick ; Däumer, Martin P. ; Walter, Hauke ; Noah, Christian ; Wolf, Eva ; Müller, Harm ; Stürmer, Martin ; Thielen, Alexander ; Kaiser, Rolf
Poster presentation: Background Maraviroc is a new drug used to treat HIV infection from the new class of drugs called CCR5 entry inhibitors. As the active principle of these drugs is to block the CCR5-receptor on the surface of the target cells, it has to be known if the virus in the patient is using only CCR5 as co-receptor or if there are populations that can also use CXCR4. Therefore, an assay to determine the tropism has to be performed before starting a therapy. Besides phenotypic assays like the TROFILE® assay by Monogram, used in the approval studies, there exist several genotyping systems like geno2pheno-coreceptor, Wetcat (providing five different genotypic tropism schemes) and WebPSSM. ...
Lerendegui-Marco, Jorge ; Guerrero Sánchez, Carlos ; Mendoza Cembranos, Emilio ; Quesada Molina, José Manuel ; Eberhardt, Klaus ; Junghans, Arnd Rudolf ; Krtička, Milan ; Belgya, T. ; Maróti, B. ; Aberle, Oliver ; Andrzejewski, Józef ; Audouin, Laurent ; Bécares, Vicente ; Bacak, Michael ; Balibrea Correa, Javier ; Barbagallo, Massimo ; Barros, Susana C.C. ; Bečvář, František ; Beinrucker, Clemens ; Berthoumieux, Eric ; Billowes, Jonathan ; Bosnar, Damir ; Brugger, Markus ; Caamaño, Manuel ; Calviño Tavares, Francisco ; Calviani, Marco ; Cano-Ott, Daniel ; Cardella, Roberto ; Casanovas Hoste, Adrià ; Castelluccio, Donato Maurizio ; Cerutti, Francesco ; Chen, Yonghao ; Chiaveri, Enrico ; Colonna, Nicola ; Cortés Rossell, Guillem Pere ; Cortés-Giraldo, Miguel Antonio ; Cosentino, Luigi ; Damone, Lucia Anna ; Diakaki, Maria ; Domingo-Pardo, César ; Dressler, Rugard ; Dupont, Emmeric ; Durán, Ignacio ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Ferreira, Pedro G. ; Finocchiaro, Paolo ; Furman, Valter ; Göbel, Kathrin ; García Ríos, Aczel Regino ; Gawlik, Aleksandra ; Glodariu, Tudor ; Gonçalves, Isabel Maria Ferro ; González Romero, Enrique Miguel ; Goverdovski, Andrey ; Griesmayer, Erich ; Gunsing, Frank ; Harada, Hideo ; Heftrich, Tanja ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Jericha, Erwin ; Käppeler, Franz ; Kadi, Yacine ; Katabuchi, Tatsuya ; Kavrigin, Pavel ; Ketlerov, Vladimir ; Khryachkov, Vitaly ; Kimura, Atsushi ; Kivel, Nikolay ; Knapová, Ingrid ; Kokkoris, Michael ; Leal Cidoncha, Esther ; Lederer, Claudia ; Leeb, Helmut ; Lo Meo, Sergio ; Lonsdale, Sarah Jane ; Losito, Roberto ; Macina, Daniela ; Marganiec, Justyna ; Martı́nez, Trinitario ; Massimi, Cristian ; Mastinu, Pierfrancesco ; Mastromarco, Mario ; Matteucci, Francesca ; Maugeri, Emilio Andrea ; Mengoni, Alberto ; Milazzo, Paolo Maria ; Mingrone, Federica ; Mirea, Mihail ; Montesano, Simone ; Musumarra, Agatino ; Nolte, Ralf ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Porras Sánchez, José Ignacio ; Praena, Javier ; Rajeev, K. ; Rauscher, Thomas ; Reifarth, René ; Riego Pérez, Albert ; Rout, Prakash Chandra ; Rubbia, Carlo ; Ryan, James A. ; Sabaté-Gilarte, Marta ; Saxena, Alok ; Schillebeeckx, Peter ; Schmidt, Stefan ; Schumann, Dorothea ; Sedyshev, Pavel V. ; Smith, Alastair Gavin ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tarifeño-Saldivia, Ariel ; Tassan-Got, Laurent ; Tsinganis, Andrea ; Valenta, Stanislav ; Vannini, Gianni ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vescovi, Diego ; Vlachoudis, Vasilis ; Vlastou, Rosa ; Wallner, Anton ; Warren, Stephen J. ; Weigand, Mario ; Weiß, Christina ; Wolf, Clemens ; Woods, Philip John ; Wright, Tobias ; Žugec, Petar
The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.
Chen, Yong Hao ; Tassan-Got, Laurent ; Audouin, Laurent ; Le Naour, Claire ; Durán, Ignacio ; Casarejos Ruiz, Enrique ; Aberle, Oliver ; Andrzejewski, Józef ; Bécares, Vicente ; Bacak, Michael ; Balibrea Correa, Javier ; Barbagallo, Massimo ; Barros, Susana C.C. ; Bečvář, František ; Beinrucker, Clemens ; Berthoumieux, Eric ; Billowes, Jonathan ; Bosnar, Damir ; Brugger, Markus ; Caamaño, Manuel ; Calviño Tavares, Francisco ; Calviani, Marco ; Cano-Ott, Daniel ; Cardella, Roberto ; Casanovas Hoste, Adrià ; Castelluccio, Donato Maurizio ; Cerutti, Francesco ; Chiaveri, Enrico ; Colonna, Nicola ; Cortés Rossell, Guillem Pere ; Cortés-Giraldo, Miguel Antonio ; Cosentino, Luigi ; Damone, Lucia Anna ; Diakaki, Maria ; Domingo-Pardo, César ; Dressler, Rugard ; Dupont, Emmeric ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Ferreira, Pedro G. ; Finocchiaro, Paolo ; Furman, Valter ; Göbel, Kathrin ; Gómez Hornillos, María Belén ; García Ríos, Aczel Regino ; Gawlik, Aleksandra ; Glodariu, Tudor ; Gonçalves, Isabel Maria Ferro ; González Romero, Enrique Miguel ; Goverdovski, Andrey ; Griesmayer, Erich ; Guerrero Sánchez, Carlos ; Gunsing, Frank ; Harada, Hideo ; Heftrich, Tanja ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Jericha, Erwin ; Käppeler, Franz ; Kadi, Yacine ; Katabuchi, Tatsuya ; Kavrigin, Pavel ; Ketlerov, Vladimir ; Khryachkov, Vitaly ; Kimura, Atsushi ; Kivel, Nikolay ; Kokkoris, Michael ; Krtička, Milan ; Leal Cidoncha, Esther ; Lederer, Claudia ; Leeb, Helmut ; Lerendegui-Marco, Jorge ; Lo Meo, Sergio ; Lonsdale, Sarah Jane ; Losito, Roberto ; Macina, Daniela ; Marganiec, Justyna ; Martı́nez, Trinitario ; Massimi, Cristian ; Mastinu, Pierfrancesco ; Mastromarco, Mario ; Matteucci, Francesca ; Maugeri, Emilio Andrea ; Mendoza Cembranos, Emilio ; Mengoni, Alberto ; Milazzo, Paolo Maria ; Mingrone, Federica ; Mirea, Mihail ; Montesano, Simone ; Musumarra, Agatino ; Nolte, Ralf ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Porras Sánchez, José Ignacio ; Praena, Javier ; Quesada Molina, José Manuel ; Rajeev, K. ; Rauscher, Thomas ; Reifarth, René ; Riego Pérez, Albert ; Robles Manzano, Maria Soledad ; Rout, Prakash Chandra ; Rubbia, Carlo ; Ryan, James A. ; Sabaté-Gilarte, Marta ; Saxena, Alok ; Schillebeeckx, Peter ; Schmidt, Stefan ; Schumann, Dorothea ; Sedyshev, Pavel V. ; Smith, Alastair Gavin ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tarifeño-Saldivia, Ariel ; Tsinganis, Andrea ; Valenta, Stanislav ; Vannini, Gianni ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vlachoudis, Vasilis ; Vlastou, Rosa ; Wallner, Anton ; Warren, Stephen J. ; Weigand, Mario ; Weiß, Christina ; Wolf, Clemens ; Woods, Philip John ; Wright, Tobias ; Žugec, Petar
The experimental area 2 (EAR-2) at CERNs neutron time-of-flight facility (n_TOF), which is operational since 2014, is designed and built as a short-distance complement to the experimental area 1 (EAR-1). The Parallel Plate Avalanche Counter (PPAC) monitor experiment was performed to characterize the beam pro↓le and the shape of the neutron 'ux at EAR-2. The prompt γ-flash which is used for calibrating the time-of-flight at EAR-1 is not seen by PPAC at EAR-2, shedding light on the physical origin of this γ-flash.