ESTRO 38 Abstract book

S358 ESTRO 38

SP-0686 Against the Motion: This house believes that immunotherapy is really changing radiation oncology Michael Baumann 1 , Nadja Ebert 2 1 German Cancer Research Center Dkfz, Radiobiology/ Radiooncology, Heidelberg, Germany 1 German Cancer Research Center Dkfz, Radiobiology/ Radiooncology, Heidelberg, Germany Abstract text In this debate arguments will be given against the motion that immunotherapy is really changing radiation oncology. In particular, it will be pointed out that clinical evidence for a breakthrough by combining radiotherapy with immunotherapy is shaky. Worse, no good biomarkers are available to predict response of immunotherapy alone, not to speak about biomarkers in the context of radioimmunotherapy. Ideas on rationales and mechanisms are plentiful, however supportive data for these ideas are rare and weak. Further details will be revealed during the debate. SP-0687 Combining Radiotherapy with Immunotherapy: focus on immunocytokines Philippe Lambin 1 , R. Lieverse 2 , E.J. Van Limbergen 3 , V Olivo Pimentel 1 , D. Marcus 2 , A. Van Der Wiel 1 , J. Theys 1 , A Yaromina 1 , L.J. Dubois 1 , A. Hoeben 4 , A.M. Dingemans 5 1 Maastricht University, Department of Radiotherapy, Maastricht, The Netherlands 2 Maastricht University, Department of Radiotherapy, Maastricht, The Netherlands 1 Maastricht University, Grow- School for Oncology And Developmental Biology, Maastricht, The Netherlands 1 Maastricht University, Department of Medical Oncology, Maastricht, The Netherlands 1 Maastricht University, Department of Pneumology, Maastricht, The Netherlands Abstract text The advent of immunotherapy is currently revolutionizing the field of oncology, where different drugs are used to stimulate different steps in a failing cancer immune response chain. Radiotherapy modifies the tumor microenvironment, causes the release of tumor (neo)antigens and immunostimulatory signals, which can enhance the effect of immunotherapy. This talk will explore the possibility of bimodal treatment combining radiotherapy with immunotherapy, in particular immunocytokines (“push the accelerator approach”) rather than checkpoint inhibitors (“release the break approach”). L19 targets the extra domain B (ED-B) of fibronectin, a marker of tumor neoangiogenesis, and can be used as immunocytokine when coupled to Interleukin 2 (IL2). We hypothesized that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is in particular dependent on ED-B expression. In summary, we have shown in several preclinical models that radiotherapy (RT) combined with L19-IL2 can induce a long-lasting antitumor effect (including a “memory effect”), dependent on ED-B expression and infiltration of cytotoxic T cells. We have shown that this effect is comparable if not superior to anti-tumor effect of checkpoint inhibitors (e.g. anti PD(L)-1) combined with single dose radiotherapy. Having recently completed a phase I safety clinical trial (NCT02086721), these promising preclinical studies will be translated to a multicentric, H2020 funded, randomized Phase II clinical study in NSCLC patients with less than 10 metastases (www.immunosabr.info, see this link for the Youtube animation: https://youtu.be/6wDE6RkrikA). References: In Press.2. Van Limbergen EJ, De Ruysscher DK, Olivo Pimentel V, Marcus D, Berbee M,

The aim of this talk is to present an overview of the current clinical evidence base, to discuss the trials in development that will provide future evidence base, and the challenges associated with clinical evaluation of technological innovation. SP-0684 MRI online ART: opportunities and pitfalls V. Valentini 1 1 Policlinico Universitario Agostino Gemelli-, Dipartimento di Diagnostica per immagini- Radioterapia Oncologica ed Ematologia, Roma, Italy Abstract text The recent introduction of the magnetic resonance guided radiotherapy (MRgRT) delivery units leads to the possibility to reduce most of the sources of uncertainty that currently influence radiation therapy treatments delivery. The more reliable visualization of the therapy volumes, achieved through the higher soft-tissue contrast provided by the MR imaging and the possibility to monitor the tumour and organs at risk (OARs) position during the treatment fraction using a high-temporal resolution MR cine imaging, address indeed the main pitfalls of standard delivery approaches. Besides these technological advances, the main advantage offered by the MRgRT is the possibility to online adapt the RT treatment plan, changing the dose distribution while the patient is still in treatment position and successfully taking into account the anatomy of the day. Aim of this talk is to describe and discuss the opportunities and pitfalls of this innovative approach, highlighting its role in managing the inter and intrafraction motion variability, the segmentation strategies to date available and the dosimetric aspects of this technique. Abstract text RT has been used for more than a century for the clinical management of virtually all cancers with extraordinary results, both in terms of side effects and efficacy. Immunotherapy is revolutionizing the clinical management of patients affected by an increasingly wide array of tumors. However, a limited percentage of patients achieve long-term clinical benefits from immunotherapy employed as a standalone treatment, calling for the development of combinatorial regimens. Radiation therapy (RT) stands out as a particularly promising candidate in this setting, reflecting not only its established safety profile, but also the potential ability of RT to mediate robust immunostimulatory effects that may synergize with immunotherapy in systemic tumor control. Combining RT with immunotherapy is a logical approach to enhance local and systemic anti-tumour immunity in locally advanced and metastatic cancers to improve outcomes in previously incurable cancer. However, optimal radioimmunotherapy regimens may call for the redefinition of conventional RT doses and fractionation schedules. We will have to redesign RT regimens for radioimmunotherapy to mediate superior efficacy in the presence of limited side effects. Revisiting doses and fractionation schedules, reducing delivery volumes, sparing both draining mymph nodes, limiting the use of cytotoxic chemotherapeutics, employing radiomics to longitudinally monitor responses. Debate: This house believes that immunotherapy is really changing radiation oncology SP-0685 For the motion: This house believes that immunotherapy is really changing radiation oncology E. Deutsch 1 1 Institut Gustave Roussy, Radiation Oncology, Villejuif, France