ESTRO meets Asia 2024 - Abstract Book

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Invited Speaker

ESTRO meets Asia 2024

Oesophageal cancer is often diagnosed at advanced stages and is associated with significant morbidity. Curative treatment includes surgical resection with or without neoadjuvant therapy and definitive chemoradiation. However, the rates of locoregional and distant recurrences remain high despite multimodality treatment. Advances in the management of oesophageal cancer have lagged behind other cancers for a long time. In contrast to other disease sites, treatment of oesophageal cancer does not differentiate between the different histological subtypes. However, recent treatment advances including improvement in radiation treatment, integration of immunotherapy to the current standard of care and a deeper understanding of the various molecular subtypes have resulted in improved clinical outcomes. We will explore the current therapeutic options for oesophageal cancer, as well as the recent updates and future directions in its management in this session.

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A review of the immune landscape in tumour development and therapy

Martin Pruschy

Radiation Oncology, University Hospital Zurich, Zurich, Switzerland

Abstract

The heterogeneity of tumor cells in a single solid tumor, in different cancer types, but also between patients with the same diagnosis, largely determines the response to radiotherapy (RT). Similarly, the heterogeneity of the tumor microenvironment, including immune cells, and systemic immunity affect tumor progression and response to different treatments. The relationship between RT and the immune system is extensively documented on the preclinical and clinical level in the context of radiation poisoning and bone marrow transplantation using total body irradiation (TBI) or large partial-body irradiation. More recently, the discovery of immunostimulatory properties of RT facilitated a large number of studies investigating the role of RT as an in situ cancer vaccine, with a potential to synergize with novel immunomodulatory agents. Surprisingly, however, there is a complete lack of (pre-)clinical insights investigating clinically relevant tumor-oriented volumes of irradiation with a stepwise increase in the coverage of the surrounding lymph nodes and normal tissue. On the preclinical level, such precise, targeted irradiation of small structures with a high-degree of inter-animal consistency is achievable thanks to the recent development of dedicated image-guided small-animal RT research platforms. Following computed tomography (CT) imaging, the treatment plan can be individually adapted to each animals’ specific anatomy, with a clear definition and quantification of target volumes and organs-at-risk. The propensity of radiotherapy to act as an in situ tumor vaccine motivated the introduction of radiotherapy- immune checkpoint inhibitor (ICI)- combinations in an attempt to overcome treatment resistance. However, a large proportion of cancers are still unresponsive to this combined treatment modality. Common practice of tumor draining lymph node irradiation might be the culprit. DLNs are the primary site of anti-tumor immune response generation and thus indispensable for the in situ vaccination effect of RT. Simultaneously, DLNs are a common site of early metastatic spread and therefore DLN sparing is not feasible in the setting of metastatic disease. Here we will present the impact of RT-induced lymphopenia and the dynamics of the immune landscape in response to tumor- and DLN-RT (alone and in combination with ICI) in multiple preclinical tumor models. At the same time, we will discuss different solutions to this challenge - with high potential to maximize the efficacy of radioimmunotherapy across different tumor types and disease stages - by implementing spatial and temporal distancing between RT of the primary tumor and RT of the DLNs, thereby maintaining an effective antitumor immune landscape.