Abstract book - ESTRO meets Asia

S22 ESTRO meets Asia 2018

Material and Methods MATLAB scripting was used to model the impact of prostate rotations on the D95% and D98% for the PTV and CTV respectively at 36 Gy for consecutive men on a SBRT prostate clinical trial (TROG 15.01 - SPARK). CTV-PTV expansion margin was 5 mm in all directions and 3 mm posterior. Translation movements were corrected before and during treatment, but rotational movements were not. Real time rotation data was acquired using KIM for the same men. A cumulative histogram analysis was performed on these rotations which showed the proportion of time that the prostate was beyond any given angle. Prostate volumes were then rotated by the range of observed angles defined by the KIM data and used to sample the 3D dose grid. These two data sets (cumulative histogram & DVH parameter versus rotation angle) were then used to determine the proportion of time during treatment that patients were within rotation angles that resulted in an acceptable DVH result. Results This analysis was performed on 19 men and 95 SBRT fractions for which all the required data was available. It was observed that there was a significantly higher average range of observed rotations around the pitch axis (maximum rotational range for each axis: pitch 28.7, roll 17.1 and yaw 14.4 degrees respectively). Consequently for the PTV this axis had the worst performance across all patients studied with only 5 out of 19 patients spending at least 90% of the beam on time across all fractions within rotation angles resulting in D95%≥36 Gy. Both the yaw and roll axes saw 14/19 patients achieving this criteria.The CTV performed significantly better with all 19 patients exceeding D98%≥36 Gy for all rotation angles observed during beam on in all three axes. Conclusion In our cohort, using current CTV-PTV margins, inter and intrafraction prostate rotations do not lead to any compromise in CTV dose delivery. Reduced PTV dosing is likely due to highly conformal treatment delivery, but is unlikely to be clinically relevant since this margin appears to be performing its role of accommodating such movements. Prostate IGRT standard of care should continue to focus on correcting any observed translational movements. The ability to further reduce CTV-PTV margins with inter- and intrafraction prostate rotational corrections could be further explored. PV-056 Dosimetric impact of uniform versus differential prostate bed expansion margins utilising IGRT E. Grierson 1 , D. Wilkinson 1 , L. Bell 1 , J. de Leon 1 1 Wollongong Hospital, Illawarra Cancer Care Centre, Wollongong, Australia Purpose or Objective Analyse the dosimetric impact & risk of geographical miss of different post-prostatectomy radiotherapy (PPRT) 6 different expansion margins were applied to a prospective cohort of 10 PPRT patients. Uniform expansion margins to superior and inferior CTV included 10mm (PTV10), 5mm (PTV5), 10mm with 5mm posteriorly (PTV10–5) and 5mm with 3mm posteriorly (PTV5-3). Differential superior and inferior CTV margins were 5mm with 10mm superior CTV anterior-posterior (AP) (PTVa5- 10) and superior prostate bed 7mm AP with 5mm elsewhere superior prostate bed and 3mm isometric inferior prostate bed (PTVa3-5-7). IMRT plans were created for each with the primary aim of matching coverage. CBCT scans were obtained the first 3 days of treatment, then weekly. CTV, rectum and bladder were contoured on each by a single investigator. CBCT were independently matched to the planning scan using bony margins based on CBCT. Material and Methods

and its deregulation is associated with several cancers including lung cancer (Lyo, 2016). Notch signaling pathway alteration leads to poor outcome and treatment resistance in patients and in preclinical models (Theys, 2013) suggesting Notch signaling as a novel therapeutic target. However, the mechanism through which Notch inhibition integrates with airway repair and cellular differentiation is not fully understood (Tsao, 2011).What is currently lacking are primary human lung tissue models that enable robust evaluation of normal tissue effects prior to clinical studies. We hypothesize that Notch inhibition has a protective effect in cells exposed to radiotherapy and may represents a potential target for intervention to modulate We established and characterized primary lung organoids and air liquid interface system (ALI), pseudo-stratified cultures derived from primary human bronchial epithelial cells (PBECs) from 6 different donors. In these cultures, basal cells proliferate and differentiate into ciliated and mucous/secretory cell types resembling the human bronchus. We irradiated lung epithelium with 2 and 4 Gy and early and late response to radiotherapy were evaluated. We investigated the consequences of blocking Notch signaling pathway using the pan-notch γ-secretase inhibitor DBZ (1uM) alone and when combined with irradiation (2, 4 Gy). Results Using immunofluorescence, western blot and q PCR we found that basal cells (p63 + , CK5 + ) cease proliferation (Ki67, EdU) at day 21 and mucous cell differentiation (Muc1/5ac + ) precedes ciliary differentiation (Ac-Tub + ) and both complete at day 28. Proliferation decreases overtime but inhibiting Notch in undifferentiated progenitors and in differentiated cells at day 21 increases p63 proliferation alone and even more in combination with radiotherapy. In all the 6 donors and in murine cultures Notch inhibition increases p63+basal progenitors and ciliated cells and decreases mucous cells alone and in combination with radiation. In irradiated cultures we observed increased pATM and pCHK2 12h and 24h post-irradiation when Notch signaling was inhibited. 53BP1 staining shows reduced DNA breaks 24h and 3 days post-irradiation when Notch was These data support the use of normal patient tissue for predictive toxicity, screening of combination treatments and disclose important novel interactions between Notch inhibition and radiotherapy. normal tissue toxicity. Material and Methods inhibited. Conclusion Poster viewing: IGRT and treatment verification (physics) PV-055 Dosimetric impact of intrafraction rotations in stereotactic prostate radiotherapy. J. Wolf 1 , J. Nicholls 1 , P. Hunter 1 , D. Trang 2 , P. Keall 2 , J. Martin 1 1 Calvary Mater Newcastle, Radiation Oncology Department, Waratah, Australia 2 University of Sydney, Radiation Physics Laboratory, Sydney, Australia Purpose or Objective Accurate delivery of radiotherapy is critical to achieving optimal treatment outcomes. Interfraction translational IGRT is now standard, and intrafraction motion management is becoming more widely accessible. Some platforms can report both translational and rotational movements in real time. The primary objective of this study is to quantify the observed intrafraction rotation of the prostate using kilovoltage intrafraction monitoring (KIM) and assess the dosimetric impact of these rotations upon both the PTV and CTV.