Albrecht, T. (Thomas)

Filtering

2022 - 20232

Settings

Author search.filters.isAuthorOfPublication.0e1b20ff-d4dd-4b80-9fec-40732fca7452

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Predictive factors for adverse event outcomes after transarterial radioembolization with Yttrium-90 resin microspheres in Europe: results from the prospective observational CIRT study
    (2023) Albrecht, T. (Thomas); Peynircioglu, B. (Bora); Munneke, G. (Graham); Arnold, D. (Dirk); Pereira, H. (Helena); Bargellini, I. (Irene); Sangro, B. (Bruno); Kolligs, F. (Frank); Bilbao, J.I. (José I.); Maleux, G. (Geert); Cianni, R. (Roberto); Jong, N. (Niels) de; Helmberger, T. (Thomas); Zeka, B. (Bleranda); Schaefer, N. (Niklaus)
    BackgroundUsing data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.MethodsWe analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).ResultsAll-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade >= 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.ConclusionOur study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.
  • Thumbnail Image
    Bcl-x(L) as prognostic marker and potential therapeutic target in cholangiocarcinoma
    (2022) Banales, J.M. (Jesús M.); Stenzinger, A. (Albrecht); Köhler, B.C. (Bruno C.); Westphalen, C.B. (Christoph B.); Albrecht, T. (Thomas); Xu, K. (Kaiyu); Illert, A.L. (Anna L.); Kelmendi, E. (Eblina); Kessler, A. (Annika); Spiekermann, K. (Karsten); Ochsenreiter, S. (Sebastian); Hübschmann, D. (Daniel); Fröhling, S. (Stefan); Springfeld, C. (Christoph); Roessler, S. (Stephanie); Hoffmeister-Wittmann, P. (Paula); Nader, L. (Luisa); Siveke, J. (Jens); Jäger, D. (Dirk); Fritzsche, S. (Sarah); Goeppert, B. (Benjamin); Brors, B. (Benedikt); Boeck, S. (Stefan); Boerries, M. (Melanie); Uhrig, S. (Sebastian); Schmitt, N. (Nathalie); Günther, M. (Michael); Bauer, S. (Sebastian); Korell, F. (Felix); Schulze-Osthoff, K. (Klaus); Kreutzfeld, S. (Simon); Horak, P. (Peter); Scherr, A.L. (Anna Lena); Sobol, B. (Benjamin); Trojan, J. (Jörg); Weichert, W. (Wilko); Hüllein, J. (Jennifer); Weiler, S. (Sofia); Glimm, H. (Hanno); Nichetti, F. (Federico); Bitzer, M. (Michael); Schirmacher, P. (Peter); Mock, A. (Andreas); Kindler, T. (Thomas); Heilig, C.E. (Christoph E.); Ormanns, S. (Steffen); Folprecht, G. (Gunnar); Klauschen, F. (Frederick)
    Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-x(L), Mcl-1) is particularly important. In this study, we investigated whether antiapoptotic protein patterns are prognostically relevant and potential therapeutic targets in CCA. Bcl-2 proteins were analysed in a pan-cancer cohort from the NCT/DKFZ/DKTK MASTER registry trial (n = 1140, CCA n = 72) via RNA-sequencing and transcriptome-based protein activity interference revealing high ranks of CCA for Bcl-x(L) and Mcl-1. Expression of Bcl-x(L), Mcl-1, and Bcl-2 was assessed in human CCA tissue and cell lines compared with cholangiocytes by immunohistochemistry, immunoblotting, and quantitative-RT-PCR. Immunohistochemistry confirmed the upregulation of Bcl-x(L) and Mcl-1 in iCCA tissues. Cell death of CCA cell lines upon treatemnt with specific small molecule inhibitors of Bcl-x(L) (Wehi-539), of Mcl-1 (S63845), and Bcl-2 (ABT-199), either alone, in combination with each other or together with chemotherapeutics was assessed by flow cytometry. Targeting Bcl-x(L) induced cell death and augmented the effect of chemotherapy in CCA cells. Combined inhibition of Bcl-x(L) and Mcl-1 led to a synergistic increase in cell death in CCA cell lines. Correlation between Bcl-2 protein expression and survival was analysed within three independent patient cohorts from cancer centers in Germany comprising 656 CCA cases indicating a prognostic value of Bcl-x(L) in CCA depending on the CCA subtype. Collectively, these observations identify Bcl-x(L) as a key protein in cell death resistance of CCA and may pave the way for clinical application.