S2993
Invited Speaker
ESTRO 2026
both on preclinical studies but also clinical experience with this class of agents [10]. In closing, I will discuss recent developments in patients with relapsed and or metastatic SCCHN with particular emphasis on EGFR-targeted strategies. Recent data relating to amivantamab, ficerafusp-alpha and petosemtamab will be discussed to consider their potential roles for future clinical implementation alongside chemoradiation approaches. References: 1. doi: 10.1056/NEJMoa2415434
radiotherapy, advocating for the integration of immune-related constraints into treatment planning and the development of multi-compartment models to guide future clinical practice.
5295 Beyond checkpoint inhibitors: Combination of RT and novel compounds Kevin J Harrington Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom Combined radiotherapy and concomitant cisplatin- based chemotherapy (CRT) is a standard-of-care for patients with locally-advanced squamous cell carcinoma of the head and neck (SCCHN). In recent years, a series of randomised phase II and III clinical trials have sought to establish a paradigm for combining immunotherapy alongside curative-intent CRT. Regrettably, multiple trials have failed to meet their primary endpoints, although sub-group analyses suggest patients with high PD-L1 CPS scores may benefit from the addition of immunotherapy to CRT. Recently, studies have shown that strategies that employ peri-operative, concomitant and adjuvant (KEYNOTE-689) [1] or pure adjuvant (NIVOPOSTOP) [2] treatment offer benefit in patients with resectable cancers. Building on the premise that concomitant immunotherapy-CRT per se does not represent the most rational way to combine these modalities, we need to examine novel approaches in which we combine agents that have the potential to maximise the benefits that accrue from both the chemoradiation and immunotherapy elements of the treatment. In this presentation, I will examine novel approaches which may have the potential to increase control of the cancer at the locoregional site, but also enhance the benefits of the immunotherapy component of treatment in protecting against both locoregional and systemic failure. First, I will review data relating to DNA repair inhibition as a means of achieving both direct cancer cell radiosensitization but also modulation of the tumour microenvironment to enhance systemic immune effects. I will focus mainly on our own work with the ATR inhibitor, ceralasertib, both in preclinical and clinical studies [3-6]. Second, I will review studies examining modulators of cell death. The data for the SMAC mimetic, Xevinapant, will be reviewed to learn the lessons of its failure [7, 8]. Subsequently, strategies to re-direct cell death towards a more necroptotic mechanism will be discussed, drawing on recently published data in immunocompetent animal models [9]. Finally, the use of innate immune activators (e.g. STING agonists) as a form of immune-boosting treatment following CRT will be discussed, drawing
2. doi: 10.1016/S0140-6736(25)01850-1 3. doi: 10.1158/1535-7163.MCT-16-0239 4. doi: 10.1158/1078-0432.CCR-18-1821 5. doi: 10.1172/JCI175369 6. doi: 10.1038/s41467-025-62249-0 7. doi: 10.1200/JCO-25-00272
8. doi: 10.1158/2767-9764.CRC-25-0604 9. doi: 10.1016/j.immuni.2024.04.025 10. doi: https://doi.org/10.64898/2026.03.23.713628
5296 The potential synergy between SFRT and immunotherapy Slavisa Tubin Radiation Oncology, University Clinic Krems, Krems, Austria Radiation is an immunomodulator. It can stimulate or suppress the immune response against cancer exerting potentially the same clinically significant impact on the efficacy of immunotherapy if combined with it. It is predicted that radiation enhances or boosts the anti-tumor effects of immunotherapy, although this is not always the case in practice. The spectrum of potentially immunostimulating effects of radiotherapy is wide. Likewise, radiotherapy can manifest numerous immunosuppressive effects. Which immunomodulatory scenario will predominate depends on numerous factors such as radiation dose, type of radiation, volume and tissue being irradiated, as well as the radiation technique used. For example, conventional radiation, which is usually performed on larger volumes over a long period of time including elective volumes (eg, non-pathological lymph nodes), usually results in immunosuppression. On the other hand, Stereotactic Body Radiotherapy and even more Spatially Fractionated Radiotherapy techniques are delivered to smaller volumes, typically in a short time- period, usually 1-3 fractions and spare better the surrounding healthy tissues and organs, including the peritumoral microenvironment, which potentially translates to immunostimulation. This lecture aims to present the existing evidence concerning the impact of radiation on the immune
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