Abstract Book

S356

ESTRO 37

efficacy of ablative (dose per fraction>7Gy) regimens. This is probably due to enhanced multi-hit effect and shorter overall treatment time. Unlike external-beam radiotherapy, interstitial high dose rate brachytherapy is delivered from the inside of the target volume. This may mean that biological effect is much beyond the linear- quadratic model conception. If doses are exceeding familiar schedules, toxicity rates, hypothetically, should be high. Data shows that genitourinary/gastrointestinal toxicity is acceptable for the salvage brachytherapy patients. In conclusion, salvage brachytherapy schedules are efficient and safe, however we need uniform approach combined with modern imaging. SP-0676 Cellular senescence: when multitasking becomes dangerous M. Demaria 1 1 University Medical Center Groningen, European Research Institute for the Biology of Ageing, Groningen, The Netherlands Abstract text Cellular senescence is a complex stress response whereby cells lose irreversibly their capacity to proliferate. Senescent cells develop the senescence- associated secretory phenotype (SASP), characterized by the expression and secretion of inflammatory cytokines, chemokines, growth factors and proteases. Cellular senescence is a potent tumor suppressive mechanism, and a desired outcome of anti-cancer therapies. However, mounting evidence indicates that senescent cells participate in multiple physiological and pathological stages, including aging and cancer. To more critically determine the diverse functions of senescent cells in vivo , we created a mouse model (p16-3MR) in which senescent cells can be detected and inducibly eliminated using the pro-drug ganciclovir (GCV). In mice, senescent cells induced by anti-cancer therapies such as radiation or chemotherapy drugs persist for several weeks in tissues and promote local and systemic inflammation. The presence of senescent cells favours growth and metastasis of different cancer models. In accordance, genetic or pharmacological removal of chronic senescent cells delays cancer progression, but also improves overall healthspan. Together, our data suggest that despite cellular senescence playing an important tumor suppressive function, accumulation and persistence of senescent cells can paradoxically contribute to deleterious effects through cell-non- autonomous effects, including cancer promotion. The balance between positive and negative roles of cellular senescence needs to be taken into account for the generation of therapies aimed at interfering with the phenotype of senescent cells. SP-0677 Radiation, Senescence and salivary glands J. Axelrod 1 1 Hadassah Medical Center, Medical centre, Jerusalem, Israel Abstract text Radiotherapy treated head and neck cancer patients commonly suffer the devastating side-effect of dry-mouth syndrome (xerostomia), which results from the irreversible loss of salivary gland function via mechanisms that are not well understood. We will present evidence from experimental models in mice and from human patients that demonstrates a fundamental role of cellular senescence in the radiation-induced loss of salivary gland function. Radiation-induced senescence, evidenced by Symposium: Radiation induced senescence

persistent DNA damage response, the expression of senescence associated markers and senescence associated secretory phenotype (SASP), including IL-6, without profound apoptosis or necrosis, closely accompanies salivary gland loss-of-function. Importantly, expression of IL-6 persists in the salivary gland long after initiation of radiation-induced DNA damage, and is crucial for both senescence and hypofunction. Similar senescence markers, including the presence of cytoplasmic chromosomal DNA, are observed in salivary glands excised from head and neck cancer patients treated with radiation. These findings indicate that cellular senescence is a fundamental mechanism driving radiation-induced salivary gland hypofunction and suggest novel strategies for its prevention. SP-0678 Stress induced senescence V. Gorgoulis 1 1 National Kapodistrian University of Athens, Histology- Embryology- Faculty of Medicine, Athens, Greece Abstract text 1. Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens, 75 Mikras Asias Str, Athens, GR-11527, Greece. 2. Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Str, Athens, GR-11527, Greece. 3. Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester, M20 4QL, UK. Premature senescence, in contrast to Replicative senescence, is a telomere-independent stress response mechanism adopted by the cell to preserve its homeostasis. Radiation induced senescence belongs to a broader entity termed stress-induced premature senescence (SISP). Apart from irradiation, SISP can be induced by a variety of stressors including oncogenes (oncogene induced senescence), DNA damage (DNA damage induced senescence), oxidative stress (oxidative stress induced senescence) and others. Stress-induced senescent cells exhibit a plethora of features and activities that are largely independent of the stimulus and will be discussed. Within this line we will present: i) an innovative biotinylated Sudan Black-B (SBB) analogue based hybrid histochemical/immunohistochemical assay (SenTraGor TM technology) that detects senescence in any biological material and ii) prototypical models of SISP to study genome and epigenome dynamics during senescence induction and senescence “escape”. SP-0679 Biological basis of radioimmunotherapy E. Deutsch 1 1 Institut Gustave Roussy, IDepartment of radiartion oncology- INSERM 1030, Villejuif, France Abstract text The immunosuppressive effects of radiation therapy have long been the only one considered. The predominant concept of a direct cell killing effect exerted on cancer cells directly, mostly though DNA damage repair and signaling processes has gained in complexity with the arousing of data underscoring the role of the tumor microenvironment into tumor’s response. Dying cancer cell may release signals which activate the surrounding immune cells, namely through the immunological cell death process. Irradiation can also increase the diversity of tumor neo antigens which are crucial to the induction Symposium: Immunotherapy