ESTRO 2021 Abstract Book

S159

ESTRO 2021

The first impression considering the available data on the interaction between radiation and the immune system in oncologic patients is controversial, as it’s showing the “bipolarity” of radiotherapy being able to exert both immunostimulatory and immunosuppressive effects. It remains unknown when one effect will prevail over the other. On the one hand, conventional radiotherapy in addition to direct cytotoxic effect to tumors, destroys also the antigen presenting cells and lymphocytes that circulate within the irradiated tumor environment shifting in that way immunogenic balance towards immunosuppression and thereby can negatively affect the overall survival. However, recently emerging evidence considering the elastic nature of this certainly complex immunomodulatory process suggest that immunosuppression can be transformed into an immune-stimulating environment by “manipulating” radiation, tumor, and immune cells, or changing the way radiotherapy, chemotherapy, and immuno-therapy are used. In terms of highly desirable radiation-induced immune-mediated anti-tumor effects, there is a large spectrum of already established immune stimulatory radiation effects including for example the dendritic cell activation, the reversal of T-cell unresponsiveness in tumor-bearing hosts, the release of immuno-stimulatory cytokines like TRAIL, TNF-α, and ceramide, or the stimulation of danger signaling pathways through the release of endogenous damage-associated molecular patterns and many others. Ideally, when, under certain circumstances, the balance is shifted toward predominant immunostimulation, these effects will result in the rejection of local and distant tumors following limited local irradiation, leading to rare phenomena known as the bystander and abscopal effects, respectively. Since this, however, does not happen on a constant basis, but rather so rarely that it calls into question whether those phenomena really exist in a clinically relevant form, many scientists have been questioned radiation immunomodulatory potential in the past and present. This is supported by the fact that radiotherapy induces also previously mentioned immunosuppression by incidentally irradiating highly radiosensitive immune cells within the tumor microenvironment and the regional lymph nodes, both of which are included in traditional radiotherapy tumor-volumes (CTV, PTV). Several studies have shown a correlation between the radiation-induced long-term lymphopenia with poorer survival, indicating that irradiation of larger volumes with multiple daily fractions can lead to global immunosuppression, negatively affecting also the ability of immune systems in mediating the radiation-induced bystander and abscopal effects. Which immunogenic scenario, “hot” or “cold”, immunostimulatory or immunosuppressive, respectively, will take place may depend on several factors, such as radiation technique, dose-fractionation or treatment volume. Conventional radiotherapy uses less immunologically effective radiation doses of 1.8-2Gy that are repeatedly delivered over a long time to the usually larger tissue volumes, often including the elective regional lymph nodes. This approach shifts immunomodulatory radiation potential toward an immunosuppressive effect. Compared to conventionally fractionated radiotherapy, several studies have shown that SBRT delivered as a high dose to small volume - thus limiting the exposure of immune cells to radiation, typically given in limited time corresponding to 1-5 days - may enhance the immune response by shifting the radiation immunomodulatory potential toward immunostimulation. Additionally, emerging unconventional radiotherapy approaches, which are delivering very high radiation dose to the partial tumor volume and thus maximizing the sparing of loco-regional peritumoral immune microenvironment, especially if delivered at precise timing according to homeostatic immune anti-tumor response fluctuations, may further improve the radiation immunogenic anti-tumor potential. This lecture will focus on the existing evidence related to immunomodulatory radiation potential, offering an insight into the interaction between radiation, cancer cells and microenvironment and the current status of the non-targeted effects of radiation.

Teaching lecture: How to tailor your cervical cancer treatment based on evidence-based dose-effect relationships

SP-0229 Does-effect relationship in the targets M. Schmid Austria

Abstract not available

SP-0230 Dose-effect relationship in the organs at risk A. Strudza Austria

Abstract not available

Teaching lecture: IAEA TRS 398: Update for modern radiotherapy

SP-0231 IAEA TRS 398: Update for modern radiotherapy H. Palmans Austria

Abstract not available

Teaching lecture: The dos and don'ts for statistical treatment outcome modelling

SP-0232 The do and don'ts for statistical treatment outcome modelling I. Vogelius Denmark