ESTRO 2024 - Abstract Book

S100 ESTRO 2024 mutations, such as EGFR and KRAS, with immunotherapy response is being explored. Circulating tumor DNA (ctDNA) holds promise in detecting molecular residual disease and predicting relapse, while radiomics allows for predictive modeling based on medical imaging data. PET-CT guidance has demonstrated its value in predicting response to treatment and optimizing radiation therapy (RT) dose-escalation strategies. These tools can refine treatment approaches and improve patient outcomes, together with RT advances such as MRI-guided RT, proton therapy, or PET-guided RT. Treatment personalization appears crucial as the ultimate goal is an uncomplicated cure for every patient. Large datasets and artificial intelligence (AI) tools can aid in patient selection and refining treatment strategies. Moreover, ongoing clinical trials and studies are generating valuable data and insights for further advancements. The future of treating unresectable stage III NSCLC lies in adopting risk-adapted and response adapted therapy approaches to improve outcomes. Invited Speaker

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Role of chromatin organisation for signalling DNA damage to innate immunity pathways

Shane M Harding

University Health Network, Princess Margaret Cancer Centre, Toronto, Canada

Abstract:

Chromatin organization plays important roles in the response to, and repair of radiation induced DNA damage. One consequence of such damage is the production of micronuclei that, depending on context, can drive chromothripsis or anti-viral gene expression programs mediated at least in part by the cGAS-STING pathway. Our data demonstrate that the nature of DNA damage determines cGAS localization and activation in micronuclei. One determinant of this localization difference is the nature of chromatin trapped in micronuclei which is dictated by chromatin states predating damage. Thus, micronuclei connect the pre-damage chromatin status and the chromatin context of the damaged genomic locus to subsequently control long-term signalling outcomes important for anti-tumour immunity. In other words, micronuclei archive contextual information about the genomic regions prone to DNA repair failure. We will present new data derived from micronuclear proteomics that uncovers features of micronuclei that determine their influence over genomic instability including deficiencies in splicing and replication stress responses. Such deficiencies presage exacerbated MN-associated DNA damage that is upstream of chromothripsis. These studies have direct implications for how cells sense and broadcast the aftermath of DNA damage during the onset of genomic instability.

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Role of DNA damage checkpoint inhibition in regulating anti-tumour immunity

Randi G Syljuåsen

Oslo University Hospital, Department of Radiation Biology, Institute for Cancer Research, Oslo, Norway

Abstract:

To combat the problem of tumor radioresistance, radiotherapy may be combined with inhibitors of DNA damage repair and cell cycle checkpoints. Emerging findings suggest that such inhibitors may also enhance antitumor