Abstract
A challenge in cancer research is the definition of reproducible, reliable, and practical models, which reflect the effects of complex treatment modalities and the heterogeneous response of patients. Proton beam radiotherapy (PBRT), relative to conventional photon-based radiotherapy, offers the potential for iso-effective tumor control, while protecting the normal tissue surrounding the tumor. However, the effects of PBRT on the tumor microenvironment and the interplay with newly developed chemo- and immunotherapeutic approaches are still open for investigation. This work evaluated thin-cut tumor slice cultures (TSC) of head and neck cancer and organotypic brain slice cultures (OBSC) of adult mice brain, regarding their relevance for translational radiooncology research. TSC and OBSC were treated with PBRT and investigated for cell survival with a lactate dehydrogenase (LDH) assay, DNA repair via the DNA double strand break marker γH2AX, as well as histology with regards to morphology. Adult OBSC failed to be an appropriate model for radiobiological research questions. However, histological analysis of TSC showed DNA damage and tumor morphological results, comparable to known in vivo and in vitro data, making them a promising model to study novel treatment approaches in patient-derived xenografts or primary tumor material.
Highlights
Radiotherapy is an integral part of anti-tumor therapy in >50% of the patients [1]
The experimental area of the University Proton Therapy Dresden (UPTD) is equipped with a horizontal beam line, making it necessary to irradiate the samples in an angular position
We described experimental setup for proton irradiation aimed reduce the number of animals neededthe to obtain meaningful results by testing thin-cut slice of organotypic brain slice cultures (OBSC), and clinically evaluated relevant endpoints regarding radiooncological cultures asOur models of high translational value for as well as fortonormal research
Summary
Proton beam radiotherapy (PBRT) has evolved as a therapy option that is relevant for pediatric cancer patients and tumors that are surrounded by critical normal tissue structures, e.g., head and neck cancers affecting the brain stem, optical nerve, parotid gland, and swallowing muscles [2,3]. The number of PBRT centers are increasing worldwide [5], additional experimental data, e.g., on combination with drugs (chemotherapy, small molecules, inhibitors), tumor microenvironment, and alternative fractionation schedules, are needed to explore the full potential of this therapy [6,7,8]. Like cancer research in general, PBRT faces the problem of defining reproducible, reliable, and practical models of tumors and normal tissues, which reflect the effects of complex treatment modalities and the heterogeneous response of patients [9]. Less extensive alternatives to standard in vivo models for organ toxicity and tumor response, which exhibit a low intra-model variation even in small sample sizes, need to be identified
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