ESTRO 37 Abstract book

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ESTRO 37

displayed ability to create xenograft models from CTCs that mirror chemotherapy response in the patient donor could also be applied to investigate radioresistance. The main limitation of using CTCs is the difficulty in filtering the small number of tumour cells from a much larger population of leucocytes. Different methods are in operation but all platforms currently must compromise between specificity and sensitivity. If this barrier can be overcome with enhanced technologies then CTC analysis may become a vital tool for clinical decision-making in radiation oncology as well as a valuable instrument for expanding our understanding of radiobiology. SP-0115 Predicting radiation toxicity: what is the link between mitochondrial DNA and individual radio sensitivity? C. Oberije 1 , M.W. Van Gisbergen 2 , E. Smeets 2 , B. Smeets 3 , P. Lambin 1 1 Maastricht University, D-Lab- GROW - School for Oncology & MCCC, Maastricht, The Netherlands 2 Maastricht University, MAASTRO lab - GROW - School for Oncology & MCCC, Maastricht, The Netherlands 3 Maastricht University, Clinical Genomics, Maastricht, The Netherlands Abstract text Improvements in imaging and radiotherapy techniques have lead to more accurate dose delivery to tumors and made it possible to spare normal tissue to a higher extent. Despite this progress, there is still a considerable group of patients who experience severe side-effects, sometimes irreversible, from treatment. Identifying these high risk patients before the start of treatment would make it possible to optimize the treatment modality. At the moment, many contributing risk factors have been investigated, but their prognostic/predictive value is limited. During this presentation we will focus on variation in mitochondrial DNA as a predictor of radiation-induced damage. Under normal physiological conditions, mitochondria produce most of the adenosine triphosphate (ATP) in the cells via the oxidative phosphorylation system (OXPHOS). ATP is important to maintain normal physiological processes but also for repair of damage. In addition, during OXPHOS reactive oxygen species (ROS) is produced, which can, together with radiotherapy induced ROS, damage cells. The mitochondrial genome (mitochondrial DNA, mtDNA) is a circular double-stranded DNA molecule and maternally inherited. As mtDNA is polyploid, a mitochondrion contains five to ten copies of mtDNA, which can differ in sequence from each other. The mtDNA encodes for 13 structural subunits of the OXPHOS chain, 2 rRNAs and 22 tRNAs necessary for the production of these subunits. Variation in mtDNA can influence mitochondrial function and the energy metabolism of cells. They have been linked to numerous diseases ranging from low-incidence life-threatening OXPHOS diseases to common neurodegenerative diseases (Alzheimer), diabetes, cancer and cardiovascular disease. Alterations in mtDNA (such as deletions, point mutations, copy number differences and non-pathogenic haplogroups) can result in mitochondrial dysfunction which can directly influence ATP, ROS production, inflammation and apoptosis. As most of these processes have been implicated in pathophysiology of radiation- induced toxicity, it is hypothesized that mtDNA variations influence normal tissue radiation response and result in radiotoxicity. We will give an overview of preclinical and clinical findings that relate mtDNA variation to radiotoxicity. The potential of mtDNA as a biomarker for individual radiosensitivity and the steps, that still need to be taken to reach this goal, will be discussed.

Joint Symposium: ESTRO-ASTRO: The art and science of head and neck radiotherapy

SP-0116 The status of reduced RT dose therapy for HPV+ cancer S. Nuyts 1 1 University Hospital Gasthuisberg, Radiation Oncology, Leuven, Belgium Abstract text Currently, all HNSCC patients are divided in two groups according to their etiology, namely the alcohol and tobacco related or the high-risk human papilloma virus (HPV) related. While worldwide, HNSCC tends to show a decrease in incidence the last decade, there is a clear rise in incidence in oropharyngeal cancers, with up to 80% of oropharyngeal cancers attributed to HPV infection. The biology of HPV positive oropharyngeal cancer is distinct: HPV contains two oncogenes E6 and E7, which inactivate the tumor suppressor p53 (TP53) and retinoblastoma protein (RB) respectively, resulting in perturbation of the cell cycle regulation. The HPV positive HNSCC distinguish from alcohol and tobacco related cancers also by distinct clinical characteristics. HPV related cancers are often diagnosed at younger age, in men with good performance status and higher socio-economic status, with advanced often cystic nodal disease, even in low T-stages. Several studies have shown that the response of HPV related disease to (chemo)radiotherapy is significantly better in comparison to the classic alcohol and tobacco related HNSCC. Notwithstanding the differences in therapy response between these two HNSCC entities, currently all locally advanced HNSCC patients are treated uniformly with organ sparing radiochemotherapy leading to a high toxicity burden. Head and neck oncologists are therefore actively exploring ways to limit toxicity related to treatment by reducing the number of treatment modalities and/or reducing intensity/dose of a given modality without compromising efficacy in these younger good prognostic patients. Many studies are underway to define de- escalation more precisely. Studies use either de- intensification of chemotherapy, de-intensification of radiotherapy or de-intensification of surgery/adjuvant therapy. Preliminary results of these studies are encouraging, but longer follow up is warranted. Further research improving our understanding of the underlying biology is needed and until mature results from prospective phase 3 clinical trials are available, de- intensification of therapy should not be performed outside a clinical trial. SP-0117 Strategies to minimize post-RT late effects on swallowing and QOL C. Nutting 1 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Test, Sutton, United Kingdom SP-0118 Innovative strategies to monitor and manage head and neck cancer patients during radiotherapy B. Chera 1 1 The University of North Carolina, Radiation Oncology, Chapel Hill NC, USA Abstract text We will discuss the use of innovative strategies to aide in the monitoring and management of head and neck cancer patients during radiotherapy. We will discuss quality improvement strategies related to the incorporation of Abstract not received