Abstract Book

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ESTRO 37

of such strategies into the routine clinical practice of radiation oncology will be discussed. SP-0114 Circulating tumour cell (CTC) analysis in radiotherapy patients A. Hudson 1 1 University of Manchester, Division of Molecular and Clinical Cancer Sciences, Manchester, United Kingdom Abstract text Circulating tumour cells (CTCs) are neoplastic cells derived from solid malignancies that can be extracted from the bloodstream. Using advanced technologies applied to a simple blood test, CTCs are isolated from the blood to provide essential information about the solid tumour from which they originate. These liquid biopsies allow genetic, proteomic, and biological assessment of tumours without the need for an invasive biopsy. Furthermore the ease and safety of CTC collection allows temporal assessment of tumour biology with minimal distress to the patient. Radiotherapy patients in particular may benefit from CTC analysis as poor performance status, co-morbidities, or location of the tumour often precludes any type of invasive biopsy in this patient population. Clinical research in different cancer subtypes has demonstrated prognostic and predictive utility for CTC counts indicating a potential for them to be used as biomarkers for treatment decisions in the future. Smaller studies have been done to assess CTC number both during and after radiotherapy with variable findings that are likely confounded by the different extraction methods used. In a research setting, capturing complete tumour cells for analysis affords potential rewards for investigating radiobiology such as the ability to assess markers of cell cycle distribution and DNA damage, receptor expression, and the co-occurrence of mutations in treatment resistance. The recently 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 haplo- groups) 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. 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 Joint Symposium: ESTRO-ASTRO: The art and science of head and neck radiotherapy