ESTRO 2020 Abstract Book

S104 ESTRO 2020

(ROS). This was supported by an increased HR capacity and a stronger activation of the intra-S phase CHK1 kinase resulting in decreased replication stress (yH2AX and RPA- Foci) after irradiation. Most strikingly, replication processes (elongation, fork stalling) were unaffected by irradiation in the radioresistant clones, indicating a pronounced role of CHK1 activated Translesion synthesis (TLS) to avoid replication-associated DNA damages. The inhibition of CHK1 and the TLS-factor RAD18 showed promising results in first experiments with a distinct radiosensitization; the most radioresistant cell line was most strongly sensitized by CHK1 or RAD18 inhibition (EF= 3) and replication processes were disrupted. Another promising target is RAD51, because METABRIC analysis of 952 TNBCs showed that CHK1, RAD18 and RAD51 are differentially expressed in tumors with high Chromosomal Instability Index (CIN) Conclusion The results presented here show that DNA repair and a stem-like phenotype are closely intertwined and that the disruption of the DNA damage response and DNA-damage- avoidance pathways are promising targets to overcome CSC radioresistance OC-0208 Comparison between 68Ga-PSMA-PET/CT and mpMRI for radiotherapy planning in primary prostate cancer S. Spohn 1 , C. Jaegle 2 , A.S. Bettermann 2 , S. Kiefer 3 , C.A. Jilg 4 , J. Kranz-Rudolph 2 , T.F. Fassbender 5 , P. Bronsert 3 , N.H. Nicolay 2 , M. Bock 6 , J. Ruf 5 , M. Benndorf 6 , A.L. Grosu 2 , C. Zamboglou 2 1 University Medical Centre Freiburg, Department of Radiation Oncology, Freiburg, Germany ; 2 University Medical Center Freiburg, Department of Radiation Oncology, Freiburg, Germany ; 3 University Medical Centre Freiburg, Institue for Surgical Pathology, Freiburg, Germany ; 4 University Medical Centre Freiburg, Department of Urology, Freiburg, Germany ; 5 University Medical Centre Freiburg, Department of Nuclear Medicine, Freiburg, Germany ; 6 University Medical Centre Freiburg, Department of Radiology, Freiburg, Germany Purpose or Objective Focal dose escalation to the gross tumor volume (GTV) in definitive radiotherapy (RT) of prostate cancer (PCa) offers the potential to further improve oncologic outcomes and is currently under investigation. Multiparametric MRI (mpMRI) is routinely used for GTV delineation but PSMA- PET/CT is emerging as a diagnostic tool to give complementary information and thus improve detection of intraprostatic tumor lesions. This study aims to intraindividually compare PSMA-PET/CT and mpMRI for delineation of GTV. Additionally, a subgroup is compared to whole mount histopathology as a reference standard. Material and Methods The data of 94 patients with primary PCa who underwent 68 Ga-PSMA-11-PET/CT and mpMRI before treatment were retrospectively examined. GTVs were manually delineated in the mpMRI (consensus contour by experts, GTV-MRI) and PET/CT (scaling SUVmin-max: 0-5, GTV-PET). The study endpoints were laterality (left/right/both lobes), cT stage and tumor volume according to the respective GTVs. Additionally, clinical parameters (age, initial PSA and Gleason score in the biopsy) were determined. Binary regression was performed to detect a putative impact of clinical parameters on the concordance between the GTV volumes. Finally, the GTVs of 17 patients were compared to histopathology of the resected specimen. Image validation was conducted on a slice by slice level in Proffered Papers: Proffered papers 10: Prostate

quadrants based on the distribution of PCa in histopathology. Results Median volume was significantly smaller in mpMRI (2.8 ml, range: 0.1- 67.7 ml) than in PSMA-PET (4.7 ml, range: 0.5 – 139.8 ml) (p < 0.0001). In 83% and 71% of patients GTVs had a difference of >25% and 50%. Laterality was different in 41% of the patients and PSMA-PET showed lesions in both lobes whereas mpMRI did not in 31% of the patients (p<0.05). Accordingly, most common cT-stage in mpMRI was cT2a (42.5%) and cT2c (53.2%) in PSMA-PET. Binary regression revealed that no clinical surrogate parameter had an impact on the concordance of the GTV volumes. The histopathologic subgroup analysis revealed a sensitivity and specificity of 86% and 87% for PSMA-PET, 58% and 94% for mpMRI and 91% and 84% for their GTV- union. Conclusion This study demonstrates in a large cohort of primary PCa patients that tumor volumes delineated in PSMA-PET/CT are significantly larger than in mpMRI. Additionally, PSMA- PET revealed lesions in both lobes in almost one third of the patients, whereas mpMIR did not. Subgroup analysis demonstrates an increased consensus of PSMA-PET with histopathology and a higher sensitivity. These results yield that PSMA-PET/CT may give augmented information for intraprostatic tumor lesion detection and thus may be the favorable diagnostic modality for focal RT. OC-0209 'SBRT and the Boost', a love story: primary endpoint analysis of the phase II hypo-FLAME trial C. Draulans 1,2 , U.A. Van der Heide 3 , K. Haustermans 1,2 , F.J. Pos 3 , J. Van der Voort van Zyp 4 , H. De Boer 4 , V. Groen 4 , E.M. Monninkhof 4,5 , R.J. Smeenk 6 , M. Kunze- Busch 6 , T. Depuydt 1,2 , R. De Roover 1,2 , S. Isebaert 1,2 , L.G.W. Kerkmeijer 4,6 1 University Hospitals Leuven, Department of Radiation Oncology, Leuven, Belgium ; 2 KU Leuven, Department of Oncology, Leuven, Belgium ; 3 The Netherlands Cancer Institute, Department of Radiation Oncology, Amsterdam, The Netherlands ; 4 University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands ; 5 University Medical Centre Utrecht, Julius Centre for Healthe Sciences and Primary Care, Utrecht, The Netherlands ; 6 Radboud University Medical Centre, Department of Radiation Oncology, Nijmegen, The Netherlands Purpose or Objective Local recurrences after radiotherapy for prostate cancer often originate at the location of the macroscopic tumour(s). Since prostate cancer cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to cope with local failure. We investigated the safety of this treatment strategy in the hypo-FLAME trial. Material and Methods Patients with intermediate or high risk prostate cancer were enrolled in a multicenter, prospective phase II trial. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric MRI-defined tumour(s). If the dose constraints to the normal tissue were at risk, these were prioritised over the aimed boost dose. The primary endpoint of the trial was treatment related acute toxicity measured by the CTCAE v4.0. Results Between April 2016 and December 2018, 100 men were treated in four academic centres. All patients were followed for a minimum of 6 months. At baseline, median age of the included patients was 73 years (range, 57-84 years), median PSA level was 10.8 ng/mL (range, 3.0-29.0