ESTRO 2022 - Abstract Book

S369

Abstract book

ESTRO 2022

GTV’s/CTV’s (prostate) during the 2.5 weeks of SMART delivery. In general, substantial reductions in GTV’s were uncommon, however, in particular for adrenal metastases a reduction of ≥ 20% was observed in 10% of the patients.

Figure 1: Average GTV/CTV deviations during the course of 5-fraction SMART delivery per tumor site

Table 1: Rate of GTV/CTV reduction during the course of SMART (fr5 versus fr1) per tumor site

Conclusion Target volume changes during a 5-fraction course of MRgRT were modest, with only a small but significant increase observed in average prostate CTV’s. A subsequent study will evaluate whether such increase is indicative for acute toxicity. A substantial reduction in GTV’s was observed for some adrenal metastases. Although the clinical relevance remains unclear, clinicians need to be aware of the potential cumulative dosimetric impact of GTV reductions when performing daily plan re-optimization.

Proffered Papers: Tumour radiobiology

OC-0425 Avoidance of DNA Replication Stress Leads to Decreased Cytosolic DNA in Breast Cancer Stem Cells

F. Meyer 1 , A. Engel 1 , L. Poole 1 , A. Krause 1 , T. Wagner 1 , A. Dubrovska 2 , C. Peitzsch 2 , C. Petersen 3 , K. Rothkamm 4 , K. Borgmann 1 1 University Medical Center Hamburg-Eppendorf, Laboratory for Radiobiology and Experimental Radiooncology, Hamburg, Germany; 2 Technical University Dresden, OncoRay, Dresden, Germany; 3 University Medical Center Hamburg - Eppendorf , Clinic for Radiotherapy, Hamburg, Germany; 4 University Medical Center Hamburg - Eppendorf , Laboratory for Radiobiology and Experimental Radiooncology, Hamburg, Germany Purpose or Objective Cancer stem cells (CSC) are a major cause for the failure of tumor therapy. This is mainly attributed to increased DNA repair capacity and immune escape. Recent studies showed that functional DNA repair via Homologous recombination (HR) avoids radiation-induced accumulation of DNA in the cytoplasm, thus inhibiting the intracellular immune response. Yet, it is unclear whether CSC suppress radiation-induced cytosolic dsDNA formation and thus suppress an innate immune response. Materials and Methods Investigations were performed in four breast cancer cell lines, their respective radioresistant clones (RR clones) which were produced by repeated irradiation (10x4Gy) and ALDH1 positive CSC, which were isolated from the RR clones. Functionality of HR was determined (plasmid reporter assay, RAD51 foci), general markers for DNA-repair (53BP1-foci) and DNA replication stress (yH2AX/RPA foci, DNA-Fiber) were analyzed. Cytosolic dsDNA formation was investigated by PicoGreen™- assay, the expression of PD-L1, PD-L2 and the activation of cGAS/STING/IRF3 via Western Blot. Radiosensitization was investigated by inhibition of ATR with the small-molecule inhibitor VE-821 in colony assays. Results A significantly increased activity of ALDH1 was observed in all RR clones and their isolated, ALDH1-positive CSC. After irradiation, survival in the RR clones was significantly increased and the number of residual 53BP1 foci was significantly decreased. This was especially apparent after irradiation in S-Phase (p<0.0001), indicating improved DNA repair by HR. This