Berlin scientists use tumor samples drawn from patients with soft tissue sarcomas to individually test their tumor response to ionizing radiation and lay one stepstone towards a translational platform for personalized radiation oncology for rare malignant

In a joint pilot study radio-oncologists Dr Siyer Roohani, PD Dr David Kaul from the Department of Radiation Oncology at Charité – Universitätsmedizin Berlin, oncologist Manuela Regenbrecht from the Sarkomzentrum Berlin-Brandenburg at Helios Klinikum Berlin-Buch and 3D cell culture experts Dr. Jürgen Loskutov, Dr. Lena Wedeken and Dr. Christian Regenbrecht from CELLphenomics cultivated tumor tissue samples from two different subtypes of soft tissue sarcomas in the laboratory and then used these so called PD3D® models for a series of radiation therapy experiments. The results were recently published in BMC Cancer.

Patient-derived 3D cell cultures (PD3D®) of sarcomas enable reproducible preclinical radiosensitivity testing
The rare occurrence of the individual subtypes as well as the biological diversity of soft tissue sarcomas make it difficult to implement large clinical studies and clinical research focused on individual subtypes. The patient-derived 3D cell cultures (PD3D®) cultivated by CELLphenomics, in this case of soft tissue sarcomas, served as a solution to these challenges in the research project, as they enable reproducible radiosensitivity analyses of the individual subtypes of soft tissue sarcomas as 3D models of the tumor of origin. In addition to sarcomas, the CELLphenomics biobank contains more than 450 patientderived 3D cell culture models of the most important types of cancer.

Aims and results of the pilot study
The aim of the joint proof of principle study was to establish a reproducible and thus reliably applicable method for testing the radiosensitivity of patient-derived 3D cell cultures of untreated, localized high-grade soft tissue sarcomas as well as to give first results on the differences of two different subtypes of soft tissue sarcomas, each exposed to different doses of photon or proton radiation.

The results are promising regarding the stability and reproducibility of the method. It could be shown that the sensitivity to ionizing radiation (both photon and proton radiation) of individual sarcomas differs significantly.

"The research results from this proof of principle study can be used as a translational platform in the future to be validated clinically and to test individualized radiation therapy plans for affected patients," explains Dr Roohani. "The goal is to translationally send the tumor sample to the laboratory for each patient, test the response of the patient-derived tumor sample to radiation, and thus make individualized statements about the potential treatment response to radiation therapy."

Publication:
The study "Photon and Proton irradiation in Patient-derived, Three Dimensional Soft Tissue Sarcoma models" and its results have been published in BMC Cancer on the 22.06.2023. Link: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11013-y

Scientists involved:
Siyer Roohani1*,†, Jürgen Loskutov2*, Jens Heufelder3,4, Felix Ehret1,5,6, Lena Wedeken2, Manuela Regenbrecht7, Rica Sauer8, Daniel Zips1,6, Andrea Denker9, Antonia M. Joussen4, Christian R. A. Regenbrecht2,10,11*, David Kaul1,6*

1 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Augustenburger Platz 1, 13353 Berlin, Germany
2 CELLphenomics GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany
3 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, BerlinProtonen am Helmholtz-Zentrum Berlin, 14109 Berlin, Germany
4 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Ophthalmology Campus Benjamin Franklin, 12200 Berlin, Germany
5 Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
6 Charité – Universitätsmedizin Berlin, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
7 Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany
8 Institute of Pathology, Helios Klinikum Emil von Behring, Walterhöferstr. 11, 14165, Berlin, Germany
9 Helmholtz-Zentrum Berlin für Materialien und Energie, Protonentherapie, 14109 Berlin, Germany
10 ASC Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany
11 Universitätsmedizin Göttingen, Institut für Pathologie, Robert-Koch-Straße 40, D-37075 Göttingen
*contributed equally