ESTRO 2020 Abstract book

S1071 ESTRO 2020

the short axis in the direction of the Bragg curve. Dosimeter positioning was verified by lasers at the surface and the digital arm was used to set the depth of dosimeters. After irradiation, dosimeters were separated, fluorescence signal read, and probability of DSB calculated. Results The probability of DSB was measured as 0.079±0.08, 0.081±0.06, 0.082±0.20, and 0.026±0.03 at depths of 15, 17, 17.5, and 18 cm, respectively. Conclusion We were able to benchmark the DNA dosimeter response in a proton beam as a function of depth. Studies to compare protons against photons are in progress. PO‐1827 Clinical application of radiation‐enhancing nanoparticles N. Scher 1 , P. Poortmans 1 , V. Calugaru 1 1 Institut Curie Ensemble Hospitalier, Paris, Paris cedex 05, France Purpose or Objective Inorganic nanoparticles (NP) activated by radiation therapy (RT) increase, in preclinical studies, radiation dose deposit within the cancer cells compared to RT alone. More recently, clinical evidence of the radiation- enhancing effects of NP begun to emerge, opening innovative fields of clinical applications in oncology. Material and Methods We performed a literature search in English and French from any year until 10 October 2019.The search term was «nanoparticle» and «radiotherapy», yielding 1270 results. Of these, we selected eleven papers related to clinical studies about the combination of RT with NP. Results Two NP are predominantly used in clinical trials: hafnium oxide and gadolinium based NP. The results of three phase 1/2 and one phase 2/3 trials all used hafnium oxide NP, involving 236 patients treated for locally advanced soft tissue sarcoma of the extremity and trunk wall, head and neck squamous cell carcinoma or liver tumours . Based on the data currently available, the safety profile seems manageable for the acute and transient immune reactions. No enhancement of the RT-related adverse events was identified. No serious adverse events were related to the intra-tumoural injection of the NP. Dispersion and migration evaluation by CT scan confirmed hafnium oxide NP to stay within the tumor without negatively impacting adjacent normal tissue or the reliability of the image- guided radiation therapy. As for treatment efficacy, the results of the only phase 2/3 trial available show that preoperative RT combined with hafnium oxide NP confirmed an increased proportion of pathological complete response compared with patients who received RT alone, possibly also related to an enhanced anti-tumour immune response. Currently, six phase 1/2 clinical trials are recruiting to evaluate the combination of gadolinium- based NP and RT for the treatment of brain metastases (NCT03818386) and cervical cancer (NCT03308604); and the combination of hafnium oxide NP and RT for the treatment of head and neck cancer (NCT01946867 and NCT02901483), liver cancer (NCT02721056), rectal cancer (NCT02465593), prostate cancer (NCT02805894) and lung cancer (NCT03589339). Conclusion Overall, available results demonstrate a safe and well tolerated toxicity profile for hafnium oxide NP, with very promising early clinical results. For gadolinium based NP, results remain pending. These data open a large field of applications and justify investing in further research. Poster: Radiobiology track: Biological therapies (e.g. viruses, vaccines)

Conclusion These results indicate the use of Abiraterone in combination with high dose x-ray radiation could potentially lead to improved tumour cell death and thus better clinical outcomes in a metastatic-castration resistant prostate cancer setting. PO‐1826 Measuring probability of double‐strand breaks along a 160 MeV Bragg curve K. McConnell 1 , L. Liu 2 , C. Chang 2 , V. Moiseenko 1 1 University of California San Diego, Department of Radiation Medicine and Applied Science, La Jolla, USA ; 2 California Protons Cancer Therapy Center, Medical Physics, San Diego, USA Purpose or Objective The linear energy transfer (LET) for a proton beam changes with depth and the biological response has been shown to change as well, with a dramatic increase at the Bragg peak. While the cellular effects of ionizing radiation (IR) are pleiotropic, it is the formation of DNA double-strand breaks (DSB) in response to IR that is the primary determinant of cell death. A correlation between production of primary damage, specifically DNA DSB, and predictive model-based cellular responses is needed to offer improved, mechanistically based treatment plan optimization. This insight will allow us to fully exploit the potential dosimetric advantages of proton beam therapy. Using a previously engineered DNA dosimeter that measures DSB as a function of physical dose, we characterized the probability of DSB as a function of depth along a 160 MeV proton beam Bragg curve. Material and Methods A Varian ProBeam pencil beam scanning proton system was used to deliver 30 Gy to DNA dosimeters placed at 15, 17, 17.5, and 18 cm depths in a SunNuclear 1D water tank using a tightly packed 10 x 10 cm spot pattern of 160 MeV. Three DNA dosimeters of 10 uL each were used at each depth and for a 0 Gy control. Dosimeters were encapsulated in a plastic tube with a 1 mm outer diameter, placed in a machined insert for the tank, and oriented with