ESTRO 2020 Abstract Book

S46 ESTRO 2020

Laboratory, Radiotherapy, Teddington, United Kingdom ; 4 University of Cambridge, Cavendish Laboratory, Cambridge, United Kingdom ; 5 Addenbrooke's Hospital, Cambridge Clinical Trials Unit, Cambridge, United Kingdom ; 6 University of Cambridge, Department of Engineering, Cambridge, United Kingdom ; 7 Addenbrooke's Hospital, Medical Physics & Clinical Engineering, Cambridge, United Kingdom ; 8 University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom Purpose or Objective Rectal toxicity remains a clinical issue in prostate radiotherapy. Associations between dose and toxicity are generally poorly understood. DVHs are commonly used to quantify dose to the rectum but have been criticised for lacking in geometric information. By evaluating spatial dose distribution to the rectal wall, stronger dose-toxicity associations may be revealed. Voxel-level analysis may indicate regions of intraorgan radiosensitivity. Furthermore, calculating motion inclusive delivered dose to the rectal wall may improve the power of predictive models. Here we compare 3D dose distributions for patients with and without toxicity to identify rectal subregions at risk (SRR) for 12 endpoints. The discriminatory ability of planned and delivered dose is compared. Material and Methods Dose to the rectal wall was calculated using biomechanical finite element modelling (Abaqus, Dassault Systèmes) for 139 prostate cancer patients. The 3D anatomical model was grown and deformed based on rectal contours either manually defined on the planning scan, or autosegmented on daily MVCT IGRT scans. Doses were calculated using CheckTomo. Dose-histories were tracked per finite element, or voxel. Patients were treated with helical IGRT and prescribed 74 Gy/37# or 60 Gy/20# (combined by converting to EQD in 37#). Total delivered dose incorporates interfraction motion and was determined by accumulating daily dose. Toxicity data were prospectively collected and cumulative incidence at 2 years post-treatment were investigated. Endpoints were: diarrhoea (26%), faecal incontinence (17 %), proctitis ≥G1 (19%) ≥G2 (14%), rectal bleeding ≥G1 (33%) ≥G2 (12%), GI toxicity ≥G1 (53%) ≥G2 (15%), stool frequency (25%), bowel bother ≥G1 (40%) ≥G2 (23%), ≥G3 (9%). Patients were split by those with and without toxicity and a voxel-wise student’s t-test was performed to identify SRRs with p<0.05 (Fig 1). Post-processing involved removing small clusters, applying a smoothing filter and filling in holes. Equivalent uniform dose (EUD) was calculated from voxels within the resulting SRR, for both planned and delivered dose. The area under the receiver operator characteristic curve (AUC) was used to indicate discriminative ability.

Conclusion Voxel-level analysis of dose to the rectal wall revealed SRRs associated with rectal toxicity. Differences between planned and delivered dose associations were small. Results may improve understanding of the pathophysiology and radiosensitivity behind radiation-induced side-effects. OC-0099 A multivariate NTCP model for GI and GU morbidity in 1151 patients treated with proton therapy J. Pedersen 1 , X. Liang 2 , C. Bryant 2 , N. Mendenhall 2 , Z. Li 2 , L.P. Muren 1 1 Aarhus University Hospital, Department of Medical Physics, Aarhus C, Denmark ; 2 University of Florida Health Proton Therapy Institute, University of Florida Health Proton Therapy Institute, Jacksonville, USA Purpose or Objective Most normal tissue complication probability (NTCP) models are derived from outcomes following photon-based radiotherapy. However, due to the fundamentally different properties between photons and protons, such as reduced dose bath and a higher relative biological effectiveness (RBE), NTCP models for photons might not be applicable to proton therapy (PT). Furthermore, most NTCP models are based on dose/volume parameters only (e.g. the probit model), but it is being recognised that also non-dose/volume related factors may be important predictors as well. The aim of this study was therefore to develop multivariate NTCP models for gastrointestinal (GI) and genitourinary (GU) morbidity for prostate patients treated with PT. Material and Methods Dose volume histogram data (DVH), for the rectum, rectal wall, bladder, and bladder wall from 1151 prostate cancer patients treated with passive scattering PT between 2006 and 2010, as well as various patient characteristics and pre-treatment factors were analysed. Prescribed target doses were 78-82 Gy (RBE=1.1) in 2 Gy fractions. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyse the effects of the studied factors on rectal and bladder morbidities. Two prospectively scored alternative grade 2 late rectal bleeding (LRB) endpoints (CTCAE v3.0) were studied: Grade 2A+2B (GR2A2B) was classified as medical and procedural (n=184 (16%)), and Grade 2B (GR2B) was classified as procedural only (n=63 (5%)). For the bladder, prospectively scored Grade 3+ GU morbidity was used as endpoint (n=51 (4%)). In the multivariate analysis we accounted for collinearity of the DVH parameters. The discriminating ability of the model was described by the

Results SRRs differed between endpoints but were all located away from the high dose region adjacent to the prostate. Accumulated dose produced stronger associations than planned dose for 9/12 endpoints (Fig 2). However, differences could not be considered significant.