ESTRO 37 Abstract book

S118

ESTRO 37

2 Maastricht Radiation Oncology MAASTRO, Radiobiology, Maastricht, The Netherlands Abstract text Advances in radiotherapy outcome for cancer treatment has mostly not been obtained from an improved fundamental insight in radiation response of normal and cancer tissues. The majority of advances stem from improved forms of high-precision beam delivery, and imaging to define tumors better and to monitor their response to therapy. Key to this is the development of highly complex treatment planning software which can produce radiation plans far surpassing human capabilities to optimize complex radiotherapy. Radiation research with animal models has not played a major role in developing current radiotherapy practice, but this may be changing rapidly now due to two new developments. On the one hand ever more sophisticated models for cancer (often orthotopic) and normal tissues have been developed recently. On the other hand, technically sophisticated research platforms are now available in nearly one hundred laboratories. These platforms combine unprecedented capabilities for precision irradiation with very small fields e.g. in an arc, with various forms of integrated onboard high resolutions imaging. These research platforms allow for the first time to perform irradiation studies at the mouse/rat level, which start to resemble the clinical standard of image- guided radiotherapy. An accurate treatment planning system for irradiating rodent models with very small beams of kilovolt photons is now available (SmART-ATP), which makes use of the onboard high-resolutions CT imager to acquire anatomical images, and of the onboard bioluminescent imager (BLI) for targeting of e.g. hypoxic regions in the tumors. Further recent technical developments are the introduction of non-coplanar beams, dual-energy CT imaging, motion-gated therapy, motion-dependent dose calculations, and recommendations on standardization of dosimetry, QA and imaging in these novel platforms (ESTRO-ACROP recommendations). In a recent study we used both the onboard CT imager and the BLI to quantify disease progression and therapy response of an implanted orthotopic glioblastoma multiforme tumor model. A strong correlation was observed between CT volume and BLI-integrated intensity. We conclude that BLI intensity can be used to monitor tumor growth but that the use of both contrast- enhanced CT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of CT and BLI for treatment planning, targeting, and monitoring. The final aim is to identify those combined novel treatments that are the most promising for clinical translation, such as radiation-induced immune response. In this work, we will report on the progress of technology development and research in this new field.

Abstract text Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. Here, aspects of PDX modelling that are relevant to these questions will be discussed. Byrne AT et al. Interrogating open issues in cancer medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Sep 15;17(10):632 SP-0225 Studying normal tissue damage using small animal high-precision irradiators P. Van Luijk 1 1 University of Groningen- University Medical Center Groningen, Radiation Oncology, Groningen, The Netherlands Abstract text Understanding radiation-induced complications is vital to the further optimization of radiotherapy treatment. With the introduction of high-precision small-animal irradiators, the field of in vivo radiobiology has regained interest and is growing. Novel high-precision irradiators offer a variety of equipment making them technologically similar, or sometimes even more advanced, than clinical machines. Though these technological advancements bring many new opportunities to the field, the rationale of their use in in vivo studies for normal tissue is not straight- forward. Using animal models is usually justified by their ability to facilitate better possibilities for controlled experiments, reduced variation in outcome measures due to better resemblance of study subjects and treatment conditions, and the possibility to test conditions beyond clinically accepted. Examples of such studies and features contributing to their clinical translation will be described. Finally, the potential of recent high-precision technology to improve and extend these studies will be discussed. SP-0226 Role of the immune system in radiation therapy M. Pruschy 1 1 University Hospital Zürich, Department of Radiation Oncology, Zurich, Switzerland Abstract text The relevance of the immune system for the radiation response of the tumor has been strongly investigated during the last decade and has been recognized to be an important determinant for the overall tumor response to radiotherapy. As such, “Tumor (R)ejection by the Immune System” might be defined as an additional “R of Radiotherapy”. Here we will outline the major general players and processes of the immune response to radiotherapy, including specific aspects related to head and neck cancer. Furthermore, we will discuss the most relevant preclinical approaches to determine and investigate the most promising combined treatment Symposium: Immunotherapy to complement chemoradiation for head and neck cancer

SP-0224 Interrogating open issues in cancer precision medicine with patient-derived xenografts A. Byrne 1 1 Royal College of Surgeons in Ireland, Physiology and Medical Physics, Dublin, Ireland