ESTRO 2020 Abstract book

S457 ESTRO 2020

limiting toxicity whilst keeping the antitumor efficiency unchanged. Though the FLASH effect has been reproduced in different tissues the underlying mechanism involved in the sparing of the healthy tissues remains to be demonstrated. To uncover the molecular and physiological mechanisms that underlie the differential response in the lung, we used a combination of transcriptomic, biochemical, immunochemical and histological in vivo and in vitro approaches and analysed the acute wound healing phase as well as late stages when fibrosis developps. Our results indicate that, compared to conventional radiotherapy, FLASH (i) induces less DNA damage, (ii) minimizes the induction of pro-inflammatory genes, (iii) limits the increase of senescent cells in the months following thoracic radiotherapy, and (iv) reduces the proliferation of progenitor cells after injury. Altogether, these results suggest that FLASH preserves the regenerative capacity of the lung. Consistent with this hypothesis, the beneficial effect of FLASH was lost in Terc - /- mice which have a deficiency in telomerase activity and harbour critically short telomeres preventing lung regeneration. The observations performed in irradiated mouse lung were confirmed in different models of primary human cells suggesting that FLASH properties could be exploited to reduce the toxicity of some radiotherapy protocols in the clinic. Abstract text Flash is a promising new treatment modality, where preclinical research has shown a reduction in toxicity for single fraction, high dose treatments at ultra-high dose rates. Most preclinical work has been done using open electron beams. The disadvantage of electron beams is the limited transmission depth and field size to treat with a homogeneous dose. Currently, linacs with photon beams cannot produce high enough dose rates for clinical Flash irradiation. Therefore scanning proton beams have been suggested as a modality that can be available on a relatively short term for clinical Flash irradiations. Ultra high dose rates up to 400 Gy/s have been achieved in a single spot of a proton beam, and delivery could be done using a scanning proton beam. However, when a plan consisting of multiple fields is delivered with such beam, the tissue is subject to a wide distribution of dose rates from the scanning beam. Although more pre-clinical work is needed to confirm that organs at risk still benefit from a Flash effect for treatment with multiple beams, a mixture of dose rates, and scanning beam that does not irradiate all tissue at once, it is important to look at the dose rate distributions of potential Flash plans. Furthermore, in order to compare different Flash experiments, we need to standardize our nomenclature in Flash to ensure that for all types of Flash delivery, whether using electrons, photons, protons, or scanned beams, it becomes clear what dose rate and dose rate distributions were used. SP-0732 Towards clinical implementation of FLASH radiotherapy M. Vozenin 1 1 Centre Hospitalier Universitaire Vaudois, Department of Radiation Oncology, Lausanne Vaud, Switzerland SP-0731 Physics treatment planning and delivery issues for FLASH Radiotherapy W. Verbakel 1 1 Amsterdam Umc, Radiation Oncology Department, Amsterdam, The Netherlands

Abstract text Radiation therapy is a cornerstone of cancer treatment and is used in over 50% of cancer patients, however its efficacy remains suboptimal in many radiation-resistant tumors. Although recent development in radiotherapy allowed higher precision and efficacy, the collateral damages to healthy tissue remain a limitation and being able to deliver high curative radiation doses to tumors depends on the ability to spare normal tissues from harmful effects of radiation. Today this goal is now at hand using FLASH-radiotherapy. FLASH-RT consists of dose delivery within an extremely short irradiation time, i.e. the dose is delivered in micro-seconds whereas with radiotherapy at conventional dose rate the dose is delivered over minutes. The main interest of FLASH-RT is its biological effect namely impressive normal tissue sparing at doses enabling remarkable tumor control, this biological effect has been called the FLASH effect by our group (review in Vozenin et al 2019). Experimental and clinical work is ongoing to understand the parameters relevant for the generation of the FLASH effect and its safe translation to the clinic. In addition, recently many groups have developed FLASH-RT program and discrepancies in findings have been reported. Several reasons can account for this discrepancy with prior results, and we would like to highlight here the critical aspects necessary for the characterization of the FLASH effect. Such considerations will hasten the development of further experimentation to move the field forward in a productive and efficient manner.

Symposium: Dose accumulation and re-irradiation for thoracic malignancies

SP-0733 Challenges and solutions for thoracic re- irradiation G. Van Tienhoven Academic Medical Center, Amsterdam, The Netherlands

Abstract not received

SP-0734 Possibilities for second breast conserving treatment after a local recurrence C. Polgár 1 1 National Institute of Oncology, Center of Radiotherapy, Budapest, Hungary Abstract text The standard treatment of early-stage breast cancer is breast-conserving surgery (BCS) and radiotherapy (RT) of the conserved breast. In spite of adequate BCS and RT, the rate of ipsilateral breast tumour recurrence (IBTR) is approximately 5-10%. Therefore, there is a need for safe and effective local salvage treatment strategies. The standard treatment for IBTR is salvage mastectomy (sMT). Other options are 2 nd. BCS with or without re-irradiation. However, the rate of 2 nd. IBTR without re-irradiation has been reported in the range of 20-30%. Thus, re-irradiation after 2 nd. BCS may decrease the chance of 2 nd. IBTR. However, re-irradiation of the whole breast with significant dose is considered inappropriate because of the high risk of serious late side effects. Due to the ability of focusing radiation dose by interstitial multicatheter brachytherapy (iBT) to a limited volume (while sparing surrounding normal tissues), iBT is a promising method to retreat the tumour bed with an effective dose after