ESTRO 37 Abstract book

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ESTRO 37

work into clinical trials that aim to improve patient outcomes. SP-0014 Systemic effects of radiotherapy: immune mechanisms, pre-clinical data and clinical evidence U. Gaipl 1 1 University Clinic Erlangen, Department of Biology, Erlangen, Germany Abstract text Radiotherapy (RT) is a common treatment for cancer and about 60% of all cancer patients will receive it during their course of illness. RT primarily aims to achieve local tumor control. The induction of DNA damage, tumor cell death and the modulation of the tumor microenvironment are the main effects of ionizing irradiation to reduce tumor masses, but also to modulate the immune system. RT might act as an in situ cancer vaccine under certain microenvironmental conditions. However, RT also fosters the upregulation of immune suppressive molecules such as the programmed cell death receptor ligand 1 (PD-L1, CD274). Ionizing radiation in general has been demonstrated to impact on the immune system and in dependence on the radiation dose particular immune modulations take place. The presentation will focus on how local irradiation changes the tumor cell phenotype and the tumor microenvironment and consecutively does impact on local and systemic changes in immune cell compositions. The dynamics of immune changes, the radiosensitivity of distinct immune cells as well as biological basis for reasonable combination of RT with immune stimulation will be discussed in detail, as well as how radiation-induced immune suppression can be overcome. Regarding the latter, the impact of radiotherapy and chemotherapy on immune checkpoint molecule expression will be outlined and possible mechanisms for that will be discussed. Based on the pre- clinical knowledge, innovative clinical study concepts of radio-immune treatments will be presented. We conclude that knowledge on immune modulations induced by ionizing radiation is important to optimize multimodal cancer therapies aiming to achieve local and systemic tumor control and to define immune-related biomarkers of radiation exposure for prognosis and prediction. SP-0015 Immunogenic cell death in radiation therapy and immunotherapy L. Galluzi 1 1 Weill Cornell Medical Center of Cornell University, Radiation Oncology, New York- NY, USA Abstract text Immunogenic cell death (ICD) is a specific variant of cell death that – in immunocompetent syngeneic s ettings – is sufficient for initiating an adaptive immune e response targeting dead cell-associated antigens. When delivered at specific doses and according to precise schedules, radiation therapy (RT) is exquisitely efficient at triggering a form of ICD that involves the timely emission of immunostimulatory molecules – including ATP and type I interferon (IFN) – from dying cells. In particular, the ICD-associated release of ATP critically depends on the activation of autophagy in irradiated cells. Thus, while autophagy inhibitors can increase the cytotoxic effects of RT against cancer cells, they also compromise the immunogenicity of RT-driven cell death, de facto decreasing its therapeutic activity (in immunocompetent hosts). Conversely, nutritional and pharmacological interventions that activate autophagy increase e the therapeutic effects of RT in preclinical tumor models. Finally, lysosomal inhibitors (which potently inhibit autophagy) failed to improve the therapeutic profile of chemotherapy and RT in a series of clinical trials testing this combinatorial paradigm.

Refined strategies are required to harness the full potential of autophagy modulators in the clinics. SP-0016 Immunocytokines the ideal immunotherapy to combine with radiotherapy? P. Lambin Maastro Clinic, Maastricht, the Netherlands

Abstract not received

Symposium: More of both? Breast reconstruction and regional lymph node irradiation!

SP-0017 Breast reconstruction: a past or present challenge for the radiation oncologist? P. Poortmans 1 1 Poortmans Philip, Radiation Oncology- Institut Curie- Paris- France, Herentals, Belgium Abstract text Since the meta-analysis of the EBCTCG published in 2005, and even more the 2011 and 2014 updates, indications for locoregional radiation therapy increased both in the post-mastectomy and the breast conserving approaches. Simultaneously, the use of breast reconstruction, either immediate or delayed, to restore the physical shape of the female breast after mastectomy increased. Both evolutions taken together increased the likelihood of a combined modality approach. However, this used in general not to be well appreciated by both reconstructive surgeons that where fearing an increased risk of complications and radiation oncologists who were confronted by a technically more challenging anatomical representation of the combination of target volumes. Notwithstanding reassuring findings about short-term safety of breast reconstruction, based on reviews of mainly retrospective single-centre experiences, controversy persists as to the long-term oncological and cosmetic outcome. This is particularly true in the case of skin- or nipple-sparing techniques. Another important issue is the precarious timing of the combination with primary or adjuvant systemic treatments, underline the huge importance of a true multidisciplinary and interactive patient-centred approach. Other current questions include the timing/sequence of surgery and radiation therapy; the preferred reconstructive method and the definition of the target volumes. SP-0018 Who might benefit most from regional nodal irradiation? A practical guide based on a publication- level meta-analysis D. Dodwell 1 1 University of Oxford, Carolyn Taylor & Paul McGale Nuffield Department for Population Health, Oxford, United Kingdom Abstract text The recent publication of the French IM, MA20 and EORTC 22922 randomized trials and the Danish Breast Cancer Group prospective cohort study have stimulated increased interest in the role of post-operative irradiation of regional nodal areas in early breast cancer. Modest benefits in outcomes were reported. To deliver these benefits and minimize late toxicity requires the use of resource-demanding radiotherapy techniques. However there are many older trials of regional radiotherapy that have not demonstrated improvements in disease-related outcomes. It is also not possible to understand which component of regional radiotherapy provides benefit as different regional nodal areas were treated within the randomized