Abstract Book

S6

ESTRO 37

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 settings – 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 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 Abstract not received Symposium: More of both? Breast reconstruction and regional lymph node irradiation!

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 radio- therapy 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 trials. Cardiac toxicity particularly from irradiation of the left sided internal mammary nodes remains a concern and the follow up of more recent trials is too probably not long enough to define this. The greater use of more effective systemic therapies, the greater prevalence of lower risk disease at presentation and improved surgical treatment mean a much improved prognosis and a lower ‘event’ rate for patients presenting today compared to those presenting within the recruitment periods for the available randomised trials. In particular patients with node negative or minimally node positive disease have a generally good prognosis and thus have less to gain from regional irradiation. A comprehensive and inclusive individual patient meta- analysis is ongoing within EBCTCG and this will better define patient and disease characteristics that allow an informed targeting of regional/IMC irradiation. The use of this treatment in patients with generally good prognosis early breast cancer including those with minimally node positive disease may not be justifiable at the present time. Risk stratification strategies need to be developed that take account of these concerns and uncertainties and allow the selection of higher risk patients most appropriately defined by nodal disease burden. SP-0019 Brother and sister: guidelines for bringing breast reconstruction and radiation therapy together. O. Kaidar-Person 1 1 Rambam Health Care Campus - Faculty of Medicine, Oncology Institute, Haifa, Israel Abstract text The use of breast reconstruction is increasing, with new surgical techniques for reconstruction aiming to improve cosmesis are constantly introduced (different location of prosthesis, use of prosthesis and flap, lipofilling, etc ). The indications for post-mastectomy radiation therapy increased over the last years. However, little is known about the oncological outcomes of these techniques and how they affect or affected by radiation therapy. Therefore, all disciplines involved in the treatment of the patient need to understand the challenges: respecting patient’s wishes without compromising oncological outcomes. The aim of this talk is to provide some guidelines to for post-mastectomy radiation therapy in