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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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Implementation of high-throughput drug screening into routine workflow for paediatric brain tumours – a single-centre experience in personalised neurooncology

Implementation eines Hochdurchsatzverfahrens zur Medikamententestung in die Routineversorgung von pädiatrischen Hirntumoren – eine monozentrische Erfahrung in der personalisierten Neuroonkologie

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  • presenting/speaker Thomas Beez - Heinrich-Heine-Universität Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Christopher Munoz-Bendix - Heinrich-Heine-Universität Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Arndt Borkhardt - Heinrich-Heine-Universität Düsseldorf, Klinik für pädiatrische Onkologie, Hämatologie und klinische Immunologie, Düsseldorf, Deutschland
  • Daniel Hänggi - Heinrich-Heine-Universität Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Guido Reifenberger - Heinrich-Heine-Universität Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland
  • Jasmin Bartl - Heinrich-Heine-Universität Düsseldorf, Klinik für pädiatrische Onkologie, Hämatologie und klinische Immunologie, Düsseldorf, Deutschland; Deutsches Krebsforschungszentrum (DKFZ), Pädiatrische Neuro-Onkogenomik, Heidelberg, Deutschland
  • Marc Remke - Heinrich-Heine-Universität Düsseldorf, Klinik für pädiatrische Onkologie, Hämatologie und klinische Immunologie, Düsseldorf, Deutschland; Deutsches Krebsforschungszentrum (DKFZ), Pädiatrische Neuro-Onkogenomik, Heidelberg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocV241

doi: 10.3205/20dgnc235, urn:nbn:de:0183-20dgnc2353

Published: June 26, 2020

© 2020 Beez et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: We have previously established and validated a highly specialized, semi-automated high-throughput drug screening (HTS) pipeline for pediatric brain tumors. Here we describe our experience in implementing this pipeline into routine workflow at a dedicated pediatric neuro-oncology center.

Methods: The pipeline is based on semi-automated devices, the D300e Digital Dispensers (Tecan Trading AG, Switzerland), that enable randomized distribution of active ingredients onto microtiter plates. It consists of 200 established chemotherapeutic agents and novel anti-cancer compounds currently in phase III and IV studies for a variety of tumor entities, not limited to brain tumors. The impact of the compounds on tumor cell viability was quantified after 72 hours of incubation using measurement of ATP level. Tumor samples of patients aged ≤18 years, who were primarily treated at our institution, were included after preoperative informed consent.

Results: Tumor samples (solid specimens and/or ultrasonic aspirator filtrate) of 164 primary tumors and 14 recurrent tumors were collected in the neurosurgical operation room and immediately transferred to the on-site laboratory, where processing and cultivation was performed. The main histological entities were pilocytic astrocytoma (N=31, 17%), medulloblastoma (N=28, 16%), glioblastoma (N=27, 15%) and ependymoma (N=21, 12%). Of these cases, 107 tumor cell cultures were established successfully and HTS was subsequently performed. Patient-specific drug screening results were categorized into absent/non-selective and selective activity of tested established chemotherapeutic agents and novel anti-cancer compounds.

Conclusion: The HTS pipeline was successfully implemented into our clinical routine workflow for pediatric brain tumors. As the tested drugs were selected for HTS based on clinical applicability, i.e. they were at least previously investigated in phase III and IV studies, personalized treatment options could be provided for 60% of pediatric brain tumors in the framework of future clinical studies.