ESTRO 2023 - Abstract Book

S573

Monday 15 May 2023

ESTRO 2023

Abstract Text Voxel based analysis (VBA) is becoming an established analysis tool in radiotherapy, allowing a deeper understanding of how the full, 3-dimensional, dose distribution affects patients’ response to radiation. VBA includes the full, complex, dose distribution in the dose-response analysis, allowing us to move away from traditional approaches which distill the dose down to a single representative value. No prior assumptions are made about anatomical dose dependence; this allows the dose to ‘talk to us’ directly, potentially identifying relationships between local dose and patient outcomes. This approach becomes more crucial as biological insights provide growing evidence pointing to heterogeneity in radiosensitivity of organs. In this presentation, we start from the position that VBA as a methodology has value, discuss best practice methodological approaches of this approach, present a roadmap to fully report and validate results, and discuss the steps to translate VBA results into the clinic for patient benefit.

Teaching Lecture: Combining immunotherapy with radiotherapy

SP-0683 Combining immunotherapy with radiotherapy T. Illidge 1 1 University of Manchester, Targeted Therapy and Oncology, Manchester, United Kingdom

Abstract Text Radiation Therapy (RT) is a highly effective anti-cancer treatment delivered to around half of all cancer patients. For most of the last century the focus was on the direct DNA damage and tumoricidal properties of RT. More recently emerging evidence suggests that RT may also have a profound immunomodulatory effect in the tumour microenvironment (TME) as well as potentially generating systemic immunity in regional lymph nodes and blood. RT has the potential to be immune-stimulatory in the form of immunogenic cell death (ICD) resulting in the release of cytokines and Damage Associated Molecular Patterns (DAMPs), that may orchestrate the recruitment of Antigen Presenting Cells (APCs), and subsequent priming and trafficking of tumour-specific T-lymphocytes into the TME and the potential generation of systemic T cell immunity. The systemic anti-tumour immunity generated from irradiating a local lesion is thought to underly the so-called ‘abscopal effect’, however this is extremely rare in routine clinical practice, which suggests that either RT rarely stimulates the immune response or that any locally induced anti-tumour immune response is immediately inhibited by the immunosuppressive nature of the TME . In contrast to these immunostimulatory effects, RT can also induce immune-suppressive responses, such as increasing the ratio of radio-resistant regulatory T-lymphocytes (Tregs), or promoting immunosuppressive immune effector cells such as macrophages and other myeloid derived cells. These immunosuppressive effects may underlie the inability of RT to promote significant systemic anti-tumour immune responses in the majority of different cancer types. This immunosuppressive TME is made up of many different immunosuppressive cells including Myeloid Derived Suppressor Cells (MDSC), Foxp3 T regulatory cells (Tregs), and immune effector cells expressing blocking inhibitory molecules such as Programmed cell death protein 1 (PD-1) or Cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4); Lymphocyte-activation gene 3, receptors and importantly surrounded by an inflammatory mileu of inhibitory cytokines including TGF- β and IL-13. Manipulating the potent immune-modulatory properties of RT in combination with immuno-regulatory agents provides a real opportunity to further improve the efficacy of RT and cancer outcomes. Indeed combining RT with immunotherapy has generated considerable interest and investment with hundreds of clinical trials designed to enhance anti-tumour responses. However the initial results from clinical trials almost exclusively combining RT with immune checkpoint inhibitors (ICI) have largely been disappointing and the reasons for these treatment failures poorly understood. Therefore, in order to make progress in enhancing RT induced anti-tumour immune responses, further investigations are required to enhance our understanding of how RT doses, fractionation and treatment volumes influence the immunomodulatory effects in the TME of different cancers. Furthermore we need to think beyond ICI to novel Immuno-oncology (IO) agents that are capable of reprogramming the immunosuppressive TME to enhance anti-tumour immune responses if improve clinical outcomes are to be achieved. In this presentation , the current progress and challenges of combining RT and immunotherapy will be outlined with an focus on novel IO agents and scheduling strategies to overcome the immunosuppressive TME in combination with RT to enhance anti-tumour immune responses.

Symposium: Adaptive radiotherapy: What do we know in 2023?

SP-0684 What are the clinical benefits of adaptive radiotherapy? O. Riou 1 1 Montpellier Cancer Institute, Radiotherapy Department, Montpellier, France

Abstract Text Adaptive radiotherapy (ART) is a recent development in radiotherapy technology and treatment personalization that allows treatment to be tailored to the daily anatomical changes of patients. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible during ART to perform a daily online adaptive process for a given patient. Therefore, ART allows a daily customization to ensure optimal coverage of the treatment target volumes with minimized margins, taking into account only the uncertainties related to the adaptive process itself. This optimization appears particularly relevant in case of daily variations in the positioning of the target volume or of the organs at risk (OAR) associated with a proximity of these volumes and a tenuous therapeutic index. ART aims to minimize severe acute and late toxicities and allows tumor dose escalation. These new developments have been possible thanks to technological development, the contribution of new multimodal and on-board imaging modalities and the integration of artificial intelligence tools for the contouring, planning and delivery of radiation therapy. Online ART is currently available on two types of radiotherapy machines: the MR-Linac and recently the CBCT-Linac. We will first describe the benefits, advantages, constraints and limitations of each of these two modalities, as