ESTRO 2020 Abstract book

S224 ESTRO 2020

of second malignancies from modern techniques has to be based on advanced modelling, accounting for the influence of many factors modulating this risk including the contribution of primary and secondary radiation, treatment margins, fractionation, imaging modalities, radiation quality etc. This presentation aims to present an overview of risk evaluations for modern forms of radiation therapy. Intensity modulated radiation therapy (IMRT) with static fields and volumetric modulated arc therapy (VMAT) have been increasingly used in recent years for their potential to create complex dose distributions suitable for sparing normal tissues for a broad range of treatment sites. The dose redistribution that characterises these treatment techniques in comparison with three-dimensional conformal radiotherapy is thought to lead to a redistribution of the risks in the irradiated tissues. Equally important to the contribution of primary radiation doses is the contribution of out of field doses from scattered radiation that has to be accounted for in risk evaluations. The changes in dose prescriptions and treatment margins associated with stereotactic body radiotherapy (SBRT) delivering high ablative doses of radiation in a limited number of fractions are other factors that can modulate the risk of second malignancies. Modelling studies have shown that the decrease of the margins between the CTV and the PTV in SBRT have direct impact onto the dose levels and heterogeneity in the normal tissues around the target and consequently on the predicted risks for second malignancies, even when accounting for interpatient anatomic variations. Furthermore, the use of flattening filter free beams could further modulate the incidence of second malignancies around the target. Protons are a further weapon in the arsenal employed in cancer radiation therapy due to their favourable dose deposition that can reduce the radiation burden in tissues around the target. Nevertheless, the sensitivity of proton dose distributions to motion and setup uncertainties and the production of secondary radiation through inelastic nuclear interactions, especially secondary neutrons with high relative biological effectiveness (RBE) that could travel far from the target, are potential concerns for this form of treatment method, also in relation to their potential to induce second malignancies. Higher doses of secondary radiation have been predicted for paediatric patients undergoing proton therapy, but the absolute magnitude of the associated risk is very low. An important contributor to the risk from all modern radiotherapy techniques is the use of imaging for patient positioning in image guided radiation therapy. The impact of this factor depends strongly on the frequency of imaging employed, as well as the modality. It is important to point out in this context that the risk contribution of many of the factors listed above is not always additive, as the response predicted from various risk models is nonlinear with dose. Furthermore, general patient characteristics, such as age and anatomy can also modulate the incidence of the risk. Other features, like genetic and lifestyle factors, comorbidities and the impact of adjuvant treatments increase the complexity of risk induction and prediction and in many cases their impact remains to be explored in the future. Proper knowledge of doses and risks delivered by various treatment modalities are essential for risk versus benefit analyses and to therefore to ensure that medical procedures are appropriately optimised. These enhance decision aid and help radiation risk communication, with the greatest possible benefit to the patient, at the lowest possible risk.

Symposium: Second malignancy after modern radiotherapy: more or less than historical precedents

SP-0386 The biology of radiation induced secondary malignancy C. Von Neubeck 1 1 Essen University Hospital, Clinic for Particle Therapy, Essen, Germany Abstract text An increasing patient number receives radiation as part of their cancer treatment. The therapy outcome improved for many cancer entities due to developments in e.g. diagnostics, imaging modalities, and radiation techniques. Patient stratification and personalized treatment based on molecular and genetic biomarkers further increased patient’s survival. However, radiotherapy has been shown to be associated with a statistically significant enhanced risk for secondary malignancies, in particular for long-term cancer survivors. The long latency period of ten and more years between radiotherapy treatment and the development of the secondary tumor impedes the evaluation of new techniques and therapies in large prospective clinical trials. Currently, there is a great uncertainty concerning the dose-response relationship and a limited understanding of the complex biological processes involved in radiation-associated carcinogenesis. However, for some factors such as incomplete DNA damage repair, genomic instability, genetic risk factors, patient age at treatment, specific organ/tissue responses, and dose-volume distributions, there is strong evidence for affecting secondary cancer risks. This talk aims to summarize current literature on risks for secondary malignancies from a biological perspective. SP-0387 Radiotherapy and second malignancy: the facts F. De Vathaire (France) Institut Gustave Roussy, Villejuif, France Abstract text Earlier detection of cancers and improved treatment methods, often employing radiation therapy, have increased the life expectancy for many cancer patients allowing at the same time a longer temporal window for the induction of second cancers. This has led to radiation therapy being described as a two-edged sword, as it can both sterilise tumour cells and induce them through the mutations they create. In light of this duality of radiation therapy, the success rates and also the risks for the induction of second malignancies have to be taken into account when choosing among the treatment options available. However, most of the knowledge on the current levels of risk comes from epidemiological studies on patients treated many decades ago with radiotherapy techniques that are no longer in use. Furthermore, setting up prospective studies of second cancers is hampered by the rapid technical developments in radiotherapy on time scales shorter than the latency times of carcinogenesis. Consequently, the evaluation of the risk for the induction Abstract not received SP-0388 Will SBRT, IMRT and protons alter the risks of second malignancy? A. Dasu 1 1 Skandionkliniken, Uppsala, Sweden