ESTRO 38 Abstract book

S344 ESTRO 38

N. Foray 1 1 U1052 Inserm - Radiobiology group- Lyon- France, Radiobiology, Lyon, France Abstract text The ATM protein is a major stress response factor involved in the DNA double-strand breaks (DSB) repair and signaling. We have recently provided evidence that the rate of the nucleo-shuttling of ATM protein was a good predictor of tissue radiosensitivity: irradiation triggers the monomerization of the abundant cytoplasmic ATM dimers, which allows the ATM monomers to diffuse in the nucleus. Once in nucleus, the ATM monomers phosphorylate the variant H2AX histone protein, which triggers the recognition of DSB and their repair via non-homologous end-joining (NHEJ) pathway. From hundreds fibroblasts derived from patients suffering from genetic disease or post-radiotherapy radiosensitivity, we have shown that delay in the nucleoshuttling of ATM may cause lack of DSB recognition, incomplete DSB repair and radiosensitivity (1- 4). A classification of radiosensitivity in three groups was proposed (5, 6): group I: radioresistance and low cancer risk, fast ATM nucleo-shuttling; complete DSB repair; group II: moderate radiosensitivity and high cancer risk, delayed ATM nucleoshuttling; incomplete DSB repair; group III: gross DSB repair defect whatever the rate of the ATM nucleoshuttling, hyper-radiosensitivity and high cancer risk with two sub-groups : sub-group IIIa (delayed ATM nucleo-shuttling, e.g. ataxia telangiectasia ( ATM mutations)); sub-group IIIb (normal ATM nucle-shuttling, e.g. the LIG4 syndrome (LIG4 mutations)) (1, 6). This model permits a relevant biological interpretation of the linear-quadratic model that links cell survival and radiation dose (7). We will ask from which threshold of DNA repair defect and ATM nucleoshuttling, a palliation in RT can be deleterious. References 1 Granzotto, A.,et al (2016). International journal of radiation oncology, biology, physics 94, 450-460 2.Belkacemi, Y. et al 2016) International journal of radiation oncology, biology, physics 96, 629-636 3.Pereira, S.,et al. (2018) International journal of radiation oncology, biology, physics 100, 353-360 4.Vogin, G., et al (2018) International journal of radiation oncology, biology, physics 101, 690-693 5.Joubert, A.,et al. (2008) International journal of radiation biology 84, 1-19 6.Bodgi, L.,et al (2013) Journal of theoretical biology 333, 135-145 7.Bodgi, L., and Foray, N. (2016) International journal of radiation biology 92, 117-131 SP-0652 The role of DNA replication stress in glioma stem cell radiation resistance R. Carruthers 1 , S. Ahmed 2 , K. Strathdee 3 , A. Chalmers 4 1 Beatson West of Scotland Cancer Centre, Clinical Oncology, Glasgow, United Kingdom; 2 University Of Sunderland, Faculty of Health Sciences and Wellbeing, Sunderland, United Kingdom; 3 University Of Glasgow, Institute of Cancer Sciences, Glasgow, United Kingdom ; 4 University of Glasgow, Institute of Cancer Sciences, Glasgow, United Kingdom Abstract text Radiation resistance and tumour recurrence are hallmarks of glioblastoma, which is one of the most aggressive human malignancies. Despite advances in the treatment of many other solid tumours, survival in glioblastoma has remained unchanged for many years, and many promising novel agents have failed to alter outcome in large phase 3 Symposium: Mechanisms of treatment resistance in glioma

radiotherapy? Where in the disease trajectory is the individual patient? 2- What are the goals of palliative radiotherapy from the perspective of the patient? And how do we match these goals with the expected toxicity and clinical outcome? 3- How do we choose between different radiation techniques and dose schedules? What is the evidence to support these choices? During the talk these issues will be discussed SP-0649 Uncertainties in single fraction treatment J. Dhont 1 1 Vrije Universiteit Brussel, IMEC-SMIT-VUB ETRO, Brussels, Belgium Abstract text Uncertainties, possible differences between the planned and delivered therapy, enter the radiotherapy treatment workflow at every step of the process.Proper identification and understanding of the extent of each uncertainty, on both a patient and treatment system level, are crucial to enable precise and accurate radiotherapy delivery. Not only to ensure sufficient target dose and minimal dose to organs at risk, but also to be certain of the dose delivered; a prerequisite for further optimization to advance radiation oncology. In case of standard fractionation, most uncertainties such as organ motion become random, blurring the planned dose around the target. Only few uncertainties are systematic after multiple fractions, often caused by wrong calibration of set-up equipment, inducing a shift of the planned dose relative to the target. To be certain of sufficient dose to the CTV despite uncertainties, PTV margins are applied. Proposed margin recipes rightly make a distinction between random and systematic errors, with higher contribution coming from the latter. However, in case of single fraction treatment, an uncertainty shift occurs. Errors such as inaccurate patient set-up no longer become random but induce a single shift in the dose with respect to the target, as systematic errors do. Only few random uncertainties remain when the total dose is delivered at once, significantly altering the PTV margin when the treatment confidence level is to remain the same. SP-0650 The Role of the RTT in the Palliative Patients Journey K. Moore 1 1 Beatson West of Scotland Cancer Centre, radiotherapy, Glasgow, United Kingdom Abstract text As radiographers become more autonomous within radiotherapy we are taking on roles that have traditionally been undertaken by the medical staff or by clinical nurse specialists. While nurses have had many years experience in consulting with the palliative patient, and many publications that describe how well this is done by our nursing colleagues there is very little in the way of evidence where a non medic/non nurse health care professional leads this type of consultation. This presentation will explore the RTT role within the palliative radiotherapy aspect of patient care and communicating the purpose of treatment. Breaking bad news to a patient or discussing where they are with regard to end of life care takes experience, confidence and most of all knowledge of treatment options and outcomes. There are models for us to refer to such as the SPIKES model, however these 3 cases will demonstrate that providing the answers to the patient questions is often fraught with more questions than answers. SP-0651 Healthy tissue response to a single fraction treatment : Impact of the individual radiosensitivity