ESTRO 2021 Abstract Book

S255

ESTRO 2021

also highly artificial since these cells are selected under major growth-promoting influences, such as serum, which generates highly proliferative tumors that no longer resemble the tumor cells from the patient. In recent years, patient-derived models of cancer, in particular patient-derived xenografts (PDX), have been identified as superior models to immortalized cell lines since PDX are maintained through in vivo serial passaging which tends to preserve both the molecular and phenotypic features of the primary tumor. Using glioblastoma (GBM) PDX as a representative model, we show that GBM PDX are much more realistic models of human disease and are useful for radiobiology research. We screened a panel of GBM PDX for radiation sensitivity and identified both inherently sensitive and resistant tumor lines (“xenolines”). We then took a cohort of inherently radiation-sensitive GBM xenolines and generated acquired radiation-resistant models through in vivo radiation over several passages in mice. Radiation-resistant xenolines were then compared to their radiation-sensitive parent xenolines using transcriptomic and kinomic methods. These studies revealed potential mediators of acquired radiation resistance which included a number of long non-coding RNA’s (lncRNA’s) that were linked to gene expression changes in DNA damage/repair that were specific to particular xenolines. Interestingly, kinomic profiling seemed to distinguish the acquired radiation-resistant xenolines from the radiation-sensitive tumors at a global level, but the major kinomic alterations were most striking for specific PDX pairs. Targeting these potential regulators of acquired radiation resistance in PDX models can help facilitate the translation of preclinical radiation research findings to the clinic.

Symposium: Multiple and multifocal SBRT in advanced disease

SP-0349 Manageable or oligometastatic disease: Evolution of terminology in radiation oncology M. Guckenberger Switzerland

Abstract not available

SP-0350 Repeat SBRT: Number of treatments, response, toxicity and patient performance S. Blamek 1 1 Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Department of Radiotherapy, Gliwice, Poland Abstract Text The safety and efficacy of stereotactic ablative radiotherapy (SABR) for extracranial lesions is well characterized and the treatment has become a first-choice procedure in several indications. Good results of the treatment prompted attempts to repeat the treatment in patients with local progression after irradiation or with new lesions in close proximity of the previously irradiated area. The set of possible clinical scenarios include also split-course treatment for oligometastases or multifocal lesions. In all these situations clinicians have to weigh the expected outcome against the risk associated with repeat irradiation of organs often prone to radiation injury or located close to other critical, dose-limiting structures. The clinical experience and relevant literature are still scarce and no commonly accepted evidence-based guidelines are available. In the current study the available clinical data on repeat SABR for the liver, lung, prostate and skeletal lesions are reviewed and summarized. The issue of tolerance doses in the setting of repeat treatment is discussed, including timing between repeated treatments, evaluation of doses accumulated in critical organs on composite histograms and spatial dose distribution reconstructions, and proposed new dosimetric parameters predictive for the risk of radiation-induced injury. Finally, actions aiming at standardization of repeated SABR procedures are proposed. Abstract Text The treatment of multifocal disease is challenging and could involve simultaneous or sequential irradiation in single- or multiple-isocenter approaches depending on the location of the lesions in the affected organ as well as to each other. Each approach has advantages and disadvantages such as the length of treatment, the number of monitor units used and hence leakage and scatter to the patient, the need for multiple setup verification before irradiation etc. Although treatments for multifocal disease are delivered in a short time interval, dose accumulation for follow up and retrospective analyses might have to account for inter- and intra-fractional corrections. These usually account for small rotations or deformations of the patient anatomy which may otherwise lead to unacceptable dosimetry when targets are located a distance from each other, as well as between fractions. Accurate dose accumulation may therefore need the registration of the planning CT with CBCT images acquired at each fraction and the subsequent accumulation of the dose according to the image registration vector or matrix. Depending on the character of correction, rigid or deformable registration may be recommended. More challenging however is the image registration and dose accumulation from the treatment of metachronous lesions especially if longer time intervals separate the treatment courses where multiple aspects have to be carefully accounted for in comparison to the case of the treatment of multifocal lesions. Thus, it is quite likely that repeated courses of SBRT may employ varying number of fractions in the different treatment courses. Furthermore, the dose distributions in each SBRT plan are highly heterogeneous, meaning that voxels in the target and the surrounding organs at risk may receive highly varying doses from each session depending on their proximity to each target. Both these aspects mean that dose distributions have to be corrected for fractionation before registration and summation, usually in the form of equivalent total doses in SP-0351 How to register images and dose from all treatment plans I. Toma-Dasu 1 1 Karolinska Institutet and Stockholm University, Medical Radiation Physics, Stockholm, Sweden