ESTRO 2020 Abstract book

S29 ESTRO 2020

process, thereby reducing overall treatment time and unnecessary imaging doses. Material and Methods The first 20 consecutive patients treated at the Centre were included in the study. Patient characteristics are recorded in Table 1. The initial IGPBT workflow consisted of: (i) 2-dimensional kilo-voltage (2DkV) image pair acquisition for gross positioning assessment, (ii) 3- dimensional cone-beam computed tomography (CBCT) acquisition to assess target volumes and organs at risk, and (iii) repeat 2DkV pair to verify translation and rotation corrections before delivering treatment. Imaging data from fractions 1-5 and then weekly [bi- weekly for head and neck treatment sites] was collated to evaluate (i) initial 2DkV imaging dose using estimated delivered dose (µGy), (ii) elapsed time between 2DkV and CBCT acquisition, and (iii) concordance of online matched values for the 2DkV and CBCT image registrations, evaluated by registration on bony anatomy and soft tissue, using ARIA OIS (v13.7, Varian Medical Systems, USA). To assess the correlation between 2DkV and CBCT image registration, data was analysed using Pearson’s Correlation Coefficient and Bland-Altman analysis.

Orthopedic Oncology, Firenze, Italy ; 4 University of Florence, Health Sciences, Firenze, Italy

Purpose or Objective Soft tissue sarcomas (STSs) are aggressive tumors with a poor prognosis that take advantage of radiotherapy. Poly(ADP-ribose) polymerase (PARP)-1 inhibitors (PARPi) enhance the cytotoxic effects of radiation. One of the most sensitive methods for monitoring radiation-induced DNA damage is detection of gamma-H2AX foci. In vitro studies in rhabdomyosarcoma showed that olaparib enhanced radiosensitivity on clonogenic assays and increased the formation of radiation-induced gamma-H2AX foci. Recently a novel method using residual gamma-H2AX foci in ex vivo irradiated tumor specimens has been developed for clinical application. The aim of the study was to assess the radiosensitizing effect of PARPi on human STSs specimens by adopting a modified ex vivo culture assays. Material and Methods Fresh tumor material was retrieved from surgical specimens from three patients with STSs. Tumors were manually cut and incubated in medium by considering 6 conditions: control, olaparib (1µM), irradiation with a single dose of 2 or 6 Gy, with or without olaparib (1µM). After irradiation, specimens were fixed in 4% formaldehyde and embedded into paraffin. In the order to evaluate the impact of olaparib inhibition on gamma-H2Ax foci formation immunofluorescence analyses were performed. Results Pathology reports revealed that samples derived from spindle cells sarcoma (2) and pleomorphic sarcoma (1). We observed that olaparib and irradiation (at both 2 and 6 Gy doses) significantly increased the mean immunofluorescence of gamma-H2AX tumor samples as compared to control in all the samples. Moreover, the combination of olaparib and radiation resulted in an increased number of gamma-H2AX foci as compared to irradiation alone, at the 6 Gy dose. Results were not different in the two histological subtypes analyzed. Ex vivo data confirmed our previous in vitro and in vivo data. Conclusion Ex vivo analysis have demonstrated that PARPi enhance radiosensitivity in STSs and have a potential role in association with radiotherapy for treatment of these aggressive tumors. We are currently recruiting more samples for analysis. Since STSs are characterized by genetic variability that overcame histological typing, we expect to find an heterogeneous response in different STSs patients. Thus, gamma H2AX analysis on ex vivo samples could represent a practical and valid test to predict response of combined treatments in order to personalize treatment. PD-0068 Streamlining the image-guided radiotherapy process for proton beam therapy: a service evaluation L. Davies 1 , L. McHugh 2 , M.C. Aznar 3 , J. Lindsay 3 , C.L. Eccles 2 1 The Christie NHS Foundation Trust, Proton Beam Therapy, Manchester, United Kingdom ; 2 The Christie NHS Foundation Trust, Radiotherapy, Manchester, United Kingdom ; 3 The University of Manchester, Division of Cancer Services, Manchester, United Kingdom Purpose or Objective Modern radiotherapy requires image-guidance to ensure precision and accuracy of treatment delivery. To implement image-guided proton beam therapy (IGPBT) at our Proton Beam Therapy (PBT) Centre, a 3-step process was developed. This study reports on an evaluation to assess the feasibility of reducing this to a 2-step imaging Poster discussion: RTT 1

Results 229 fractions were evaluated (per patient: range 8-19, median 10). 19 (8.3%) fractions required patient repositioning following the initial 2DkV. Using a 2-step imaging process would reduce the imaging dose by 3.4mGy on average for all patients over a whole treatment course. The use of the 3-step process required a mean additional time of 5.1 minutes (range: 3.3 to 9.9) compared to the 2- step process. Overall image results indicated that correspondence between the mean displacements from the initial 2DkV and CBCT images for all treatment sites was high, with R=0.94, 0.94 and 0.80 in the anterior-posterior, superior-inferior and right-left directions respectively. Bland-Altman analysis showed there was very little bias and narrow limits