ESTRO 2022 - Abstract Book

S156

Abstract book

ESTRO 2022

Currently, many clinical studies are undertaken to investigate the effectiveness of radio-immune combinations (RIC), with the early results showing mixed success. In NSCLC, a combined analysis of two phase 2 trials (PEMBRO-RT and MDACC) did show improved effectivity of checkpoint inhibitors when combined with radiation. On the other hand, the CHEERS trial investigated the addition of SBRT to PD-(L)1 in a variety of tumours, with no effect on PFS. Furthermore, a trial investigating SBRT in addition to IL2 treatment over IL2 alone failed to show improvements in PFS and OS in patients with metastatic melanoma. These mixed results unfortunately show there is still a long way to go before RIC can become part of routine clinical practice. Additionally, important questions remain unanswered, including: (1) how representative are the results of preclinical models for patients in this context; (2) what are the exact molecular pathways and biomarkers that determine or predict a successful RIC response in humans; (3) what is the ideal sequencing of radiotherapy along with the different forms of immunotherapy in humans; (4) what should be the ideal fraction dose to trigger an abscopal immune response in a specific clinical context; (5) how detrimental is unwanted dose to the draining lymph nodes, blood pool and/or bone marrow to RIC responses? Given this context, combining brachytherapy with immunotherapy holds some very interesting and unique opportunities. First of all, in contrast to all other forms of radiotherapy, due the nature of the interstitial procedure, brachytherapy allows direct intra-tumoral access. On the one hand, this means access to tumour tissue, through which the biologic and immuno- modulary effects of radiation can be directly evaluated in human , and in multifaction treatments even in a time dependent manner . On the other hand, interstitial access would also allow the injection of immunotherapeutic agents locally to evaluate its biological effects, in human . Local injection could also allow the treating clinician to bypass the systemic effects of immune treatments in order to minimize associated toxicity. This is particularly interesting for older drugs like IL-2, which, although effective, currently suffer from declined use due to severe systemic toxicity. Is it has been clearly demonstrated in the past that in order to induce an efficient abscopal immune response, it is essential to ensure the correct fraction dose. However, this specific dose may be very difficult to determine, as it has been shown to be context dependent. Therefore, a better approach might be to bypass this problem, for example through clever design of a heterogeneous dose profile, in order to achieve a wide range of doses all at once . Brachytherapy, as a result of its very inhomogeneous dose distribution, might be better suited to such an approach rather than other radiotherapy techniques. Brachytherapy can also offer dose delivery with unique dose rates , like VLDR, LDR and PDR next to HDR. Although the immunogenic effects of different dose rates have only been poorly examined, some preliminary results are interesting. A final specific advantage of brachytherapy is its unsurpassed ballistic selectivity, allowing great target coverage while avoiding a low dose irradiation bath to the surrounding tissues. As essential components of the adaptive immune response, like naïve T-cells, are very sensitive to low doses of radiation, it has been hypothesized that limiting the low dose volume to the blood pool, bone marrow or lymph nodes, might be very beneficial for RIC setups.

SP-0184 Impact of radiation dose and field size on immune responses

A.Sharabi

USA Abstract not available

Symposium: Emerging radiobiological modifiers

SP-0185 Role of serine/glycine metabolism in radioresistance

K. Kampen

1 The Netherlands Abstract not available

SP-0186 Nanomedicine in radiotherapy: Potential, challenges and emerging technologies

K. Prise 1

1 Queen's University Belfast, Patrick G Johnston Centre for Cancer Research, Belfast, United Kingdom

Abstract Text The major goal of all radiotherapy is to maximise the therapeutic index by efficient killing of tumour cells whilst protecting normal tissues. It has long been thought that the development of nanomedicine approaches, using metal-based nanoparticles can contribute to this, by acting as radiosensitising agents alongside being used as imaging agents, so called theranostics. For many years, significant effort has been focussed on the development of particularly gold-based nanoparticles. Our radiation physics understanding of how gold nanoparticles sensitise cells to radiation has moved from an assumption that mass attenuation coefficients of metal NP effects are critical to also including the importance of localised auger electron cascades around the nanoparticle. This has important implications for nanoparticle selections and sensitisation effects seen with different types of clinical radiations including high energy photons and ion beams. In general, however there is still significant gaps in our knowledge around the optimal chemistry around nanoparticles, their uptake mechanisms, bioavailability and cellular/tissue distributions. Overall, in many experimental studies significant biological sensitisation is observed beyond that predicted by known physical enhancement mechanisms. Despite our gaps in knowledge, a vast range of nanoparticle types have been assessed pre-clinically, including gold and iron-based nanoparticles but the most encouraging to date, which have reached clinical testing, are a hafnium oxide-based particle (NBTXR3) and a gadolinium-based nanoparticle (AGuIX). AGuIX is now in clinical trials for patients with multiple metastatic brain tumours showing good bioavailability and little toxicity. Crucially it appears to be effective even