@article{IsbernerKrausGrigoleitetal.2021,
  author    = {Isberner, Nora and Kraus, Sabrina and Grigoleit, G{\"o}tz Ulrich and Aghai, Fatemeh and Kurlbaum, Max and Zimmermann, Sebastian and Klinker, Hartwig and Scherf-Clavel, Oliver},
  title     = {Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial},
  series = {Cancer Chemotherapy and Pharmacology},
  volume    = {88},
  journal   = {Cancer Chemotherapy and Pharmacology},
  number    = {6},
  issn      = {1432-0843},
  doi       = {10.1007/s00280-021-04351-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266476},
  pages     = {973-983},
  year      = {2021},
  abstract  = {Purpose Knowledge on Ruxolitinib exposure in patients with graft versus host disease (GvHD) is scarce. The purpose of this prospective study was to analyze Ruxolitinib concentrations of GvHD patients and to investigate effects of CYP3A4 and CYP2C9 inhibitors and other covariates as well as concentration-dependent effects. Methods 262 blood samples of 29 patients with acute or chronic GvHD who were administered Ruxolitinib during clinical routine were analyzed. A population pharmacokinetic model obtained from myelofibrosis patients was adapted to our population and was used to identify relevant pharmacokinetic properties and covariates on drug exposure. Relationships between Ruxolitinib exposure and adverse events were assessed. Results Median of individual mean trough serum concentrations was 39.9 ng/mL at 10 mg twice daily (IQR 27.1 ng/mL, range 5.6-99.8 ng/mL). Applying a population pharmacokinetic model revealed that concentrations in our cohort were significantly higher compared to myelofibrosis patients receiving the same daily dose (p < 0.001). Increased Ruxolitinib exposure was caused by a significant reduction in Ruxolitinib clearance by approximately 50\%. Additional comedication with at least one strong CYP3A4 or CYP2C9 inhibitor led to a further reduction by 15\% (p < 0.05). No other covariate affected pharmacokinetics significantly. Mean trough concentrations of patients requiring dose reduction related to adverse events were significantly elevated (p < 0.05). Conclusion Ruxolitinib exposure is increased in GvHD patients in comparison to myelofibrosis patients due to reduced clearance and comedication with CYP3A4 or CYP2C9 inhibitors. Elevated Ruxolitinib trough concentrations might be a surrogate for toxicity.},
  language  = {en}
}
@article{RadeloffRamosTiradoHaddadetal.2021,
  author    = {Radeloff, Katrin and Ramos Tirado, Mario and Haddad, Daniel and Breuer, Kathrin and M{\"u}ller, Jana and Hochmuth, Sabine and Hackenberg, Stephan and Scherzad, Agmal and Kleinsasser, Norbert and Radeloff, Andreas},
  title     = {Superparamagnetic iron oxide particles (VSOPs) show genotoxic effects but no functional impact on human adipose tissue-derived stromal cells (ASCs)},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {2},
  issn      = {1996-1944},
  doi       = {10.3390/ma14020263},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222970},
  year      = {2021},
  abstract  = {Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.},
  language  = {en}
}
@article{TamihardjaLutyjKraftetal.2021,
  author    = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis},
  series = {Frontiers in Oncology},
  volume    = {11},
  journal   = {Frontiers in Oncology},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2021.764536},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992},
  year      = {2021},
  abstract  = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.},
  language  = {en}
}
@article{ToppvanMeertenHouotetal.2021,
  author    = {Topp, Max S. and van Meerten, Tom and Houot, Roch and Minnema, Monique C. and Bouabdallah, Krimo and Lugtenburg, Pieternella J. and Thieblemont, Catherine and Wermke, Martin and Song, Kevin W. and Avivi, Irit and Kuruvilla, John and D{\"u}hrsen, Ulrich and Zheng, Yan and Vardhanabhuti, Saran and Dong, Jinghui and Bot, Adrian and Rossi, John M. and Plaks, Vicki and Sherman, Marika and Kim, Jenny J. and Kerber, Anne and Kersten, Marie Jos{\´e}},
  title     = {Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma},
  series = {British Journal of Haematology},
  volume    = {195},
  journal   = {British Journal of Haematology},
  number    = {3},
  doi       = {10.1111/bjh.17673},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258342},
  pages     = {388-398},
  year      = {2021},
  abstract  = {Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel-related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 106 anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93\% and 61\%, respectively (grade ≥ 3, 2\% and 17\%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14·8 months, objective and complete response rates were 73\% and 51\%, respectively, and 51\% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.},
  language  = {en}
}