ESTRO 38 Abstract book

S19 ESTRO 38

Definitive results after closing of recruitment in this phase II randomized trial are awaited. The presentation will focus on the findings related to the occurrence of acute toxicity and late mucosal ulcers, the latter being the identified dose-limiting factor for further dose-escalation. SP-0052 Heterogeneous dose adapted to treatment response during radiotherapy: clinical experience from cervix cancer IGABT I. Jürgenliemk-Schulz 1 1 UMC Utrecht, Radiation Oncology, Utrecht, The Netherlands Abstract text For many decades, technological developments in cervix cancer brachytherapy have been limited and treatment was based on 2D imaging and standard approaches as developed by the classical brachytherapy schools in the early 20th century. With ICRU38 a system for dose prescription and reporting became available; mainly based on X-ray determined applicator related dose points. In recent years, image guided adaptive brachytherapy (IGABT) has resulted in a major change of practice. The ICRU89/GEC-ESTRO recommendations support the introduction of IGABT. They are based on repetitive tumour assessment through clinical examination and imaging, preferably magnetic resonance imaging (MRI), with adaptation of dose according to the tumour extent at diagnosis, and the response to EBRT at the time of brachytherapy. Adaptive treatment planning takes into account the changes during treatment and prescribes specific doses to the various volumes of interest. For the primary tumour adaptive target volumes can in principle be defined after any treatment phase. The residual GTV reflects macroscopic tumour rest whereas the adaptive CTV takes into account the morphology and topography of the initial GTV and the morphologic and/or functional response to treatment. For definitive cervical cancer radiotherapy, these volumes are boosted through brachytherapy to different dose levels according to estimated levels of remaining tumour cell burden and in order to achieve very high doses in defined small volumes. Several mono-institutional studies and the prospective multicentre international RetroEMBRACE and EMBRACE studies have demonstrated that a highly differential dose distribution with significant dose escalation is clinically feasible with IGABT in cervical cancer. This is because with IGABT, the “super-high” doses are only administered to small volumes. The response-adaptation of volume is the key factor to identify volumes which are small enough to tolerate such high doses. The excellent outcome of IGABT has been demonstrated in several mono- institutional reports as well as in the RetroEMBRACE study. The 3-year local and pelvic control rates reached 98–100% and 96%, respectively, for FIGO stage IB1 and IB2 disease, and 93–96% and 89–91%, respectively, for stage IIB disease. For stage III/IVA disease, the local and pelvic control rates between centres were more variable ranging from 73–86%. Comparing with data as published after (chemo)radiation and traditional brachytherapy for cervical cancer the estimated gain of IGABT in its early phase is about 10% for pelvic/local control and not to the cost of additional morbidity. Further fine tuning the therapeutic window of IGABT can be expected as our knowledge on dose levels needed for better control and less morbidity is constantly increasing. Evidence for clinical improvement in terms of local/pelvic control will be the main focus for this presentation but the way to achieve this will also be addressed. SP-0053 Exploiting low drug uptake volume for dose painting A. Yaromina 1 , L. Dubois 1 , P. Lambin 1

from imaging data has to cope with incomplete information and temporal changes, effectively degrading both image sensitivity and specificity. The combination of multiple imaging modalities (increase overall sensitivity) and multiple examinations to quantify therapy response (increase overall specificity) can remedy this, and seems to be the most promising route to DP. In practice, it could turn out very difficult to prove the non-inferiority of DP versus a SIB of equal dose. However, at the very least, any imaging modality that is shown to have predictive value stratifies patients into risk groups and can therefore be the basis of patient-specific dose prescriptions, be they applied as SIB or DP. Notwithstanding the difficulties with an evidence base for DP from the tumour control perspective, normal tissue sparing might be the strongest rationale. SP-0051 What are the limitations on dose escalation to sub-volumes in head and neck cancer: experience from dose painting F. Duprez 1 , J. Daisne 2 , W. de Gersem 1 , I. Goethals 3 , L. Olteanu 1 , T. Vercauteren 1 , W. de Neve 1 1 Universitair Ziekenhuis Gent, Radiotherapie‐Oncologie, Gent, Belgium ; 2 UCL‐CHU Namur, Radiotherapie, Namur, B Belgium; 31 Universitair Ziekenhuis Gent, Nuclear Medicine, Gent, Belgium Abstract text Dose escalation of radiotherapy above 70 Gy could potentially lead to higher locoregional control rates but is hampered by severe acute and late toxicities. Molecular imaging based dose-painting is an attractive concept for dose-escalation while keeping toxicity lower to equal. As per-treatment changes of anatomical as well as biological signal intensity often occurs, these techniques are mostly performed in an adaptive radiotherapy program, using re- imaging during the 7-weeks of radiotherapy. Many theoretical as well as planning studies have been performed employing the dose-painting concept, broadly investigating two molecular imaging dose-painting methods: (1) dose painting by contours (DPBC): using discretely contoured subvolumes within the tumor based on molecular imaging. (2) dose painting by number (DPBN): using molecular imaging voxel-intensities to directly optimize radiotherapy plans. In contrast to the relatively high number of planning studies, few clinical trials have been performed. The research program for head and neck radiotherapy at Ghent University Hospital has been focusing on molecular based dose-painting since 2003. Consecutively, following prospective clinical trials have been performed, all of them based on 18 F-FDG-PET: (1) 2003-2005: phase I, non-adaptive DPBC in fractions 1 -10 of 32; n = 41.(2) 2007-2009: phase I, 2-phase adaptive DPBN in fractions 1-20 of 32; n = 21. (3) 2010-2011: feasibility trial on 3-phase adaptive DPBN in fractions 1-30/30; n = 10. (4) 2012-2014: feasibility trial on 3-phase adaptive DPBN in fractions 1-30/30 for reirradiation of recurrent head and neck cancer; n = 10. (5) 2011-2018: phase II randomized trial comparing 3- phase adaptive DPBN in fractions 1-20/30 with standard non-dose painting, non-adaptive IMRT; n = 95. Trials 2-3-4 demonstrated the feasibility of biological imaging based dose-painting in head and neck cancer. However, during the randomized phase II trial, the DPBN- dose prescription has been adapted twice due to an unanticipated high occurrence of late mucosal ulcers: at the last interim analysis available at time of abstract writing, 9/39 studied patients developed late grade 4 mucosal ulcers, that seemed to be strongly associated not only with the high-dose subvolumes, but also with continuation of smoking or alcohol drinking after DPBN.