ESTRO 2024 - Abstract Book

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Invited Speaker

ESTRO 2024

The Institute of Cancer Research, Division of Radiotherapy and Imaging, London, United Kingdom

Abstract:

Cancer cells frequently acquire a state of genomic instability that can be achieved through mutational and non mutational alterations in DNA repair pathways. This allows tumours to undergo clonal evolution and acquire characteristics that can result in therapy resistance. Paradoxically, genomic instability can serve both as a driver of poor outcomes for patients but also as a novel therapeutic opportunity for oncologists who may be able to exploit specific synthetically lethal vulnerabilities in cancer cells with aberrant DNA repair capacity. Such therapeutic opportunities include targeting ataxia telangiectasia and Rad3-related (ATR) kinase as a potentially cancer-selective approach. Small molecule inhibitors of ATR can serve as potent cancer cell-targeted radiosensitisers, but their effects can also be manifest in the tumour microenvironment where they can drive innate and adaptive immune responses against tumour cells. In this presentation, data on the cancer cell-specific radiosensitising effects of ATR inhibition will be outlined. Subsequently, the pro-inflammatory effects of radiotherapy plus ATRi will be reviewed, focusing on published and unpublished data from preclinical studies of combinations with immune checkpoint blockade (anti-PD-L1, anti-TIGIT and anti-NKG2A antibodies). In addition, recently published data on the immune effects of single-agent treatment with the ATR inhibitor, ceralasertib, from our completed clinical PATRIOT trial (parts A and B) will be presented (Dillon et al. J. Clin. Invest. 2024;134:e175369. doi: 10.1172/JCI175369). Finally, unpublished data on combining radiotherapy with ceralasertib in patients with a range of tumour types from our PATRIOT (part C) study will be reviewed.

3431

Motion-management challenges and strategies in proton therapy for liver tumours

Lene Joergensen

Aarhus University Hospital, Danish Center for Particle Therapy, Aarhus, Denmark

Abstract:

Liver tumors are highly prone to intrafractional motion due to respiratory motion and deformation of the liver due to positional changes and movements of other abdominal organs during treatment. This leads to several motion management challenges during both treatment planning and the daily treatment of the patient. Proton therapy is a high-conformal treatment modality and, hence, highly sensitive to target motion during treatment. Thus, treating targets prone to intrafractional motion using proton therapy requires well-established motion management strategies. The Danish Center for Particle Therapy (DCPT) treats patients with primary liver tumors (hepatocellular carcinoma, HCC) using exhale-gated proton therapy. The patients are treated within a Danish national phase II study for hepatocellular carcinoma (HCC). The overall aim of this study is to investigate the safety of treating patients with large liver tumors (up to 12cm) and/or impaired liver function (maximum Child-Pugh B8) using exhale-gated proton therapy. These patients have no other curative treatment possibilities. To safely treat these patients, it is crucial to spare non-involved liver tissue from radiation dose, due to the impaired liver function of these patients and/or the size of the liver tumor. This emphasizes the importance of effective management of intrafractional motions.