P03.14.A DUMMY RUN QUALITY ASSURANCE STUDY IN THE ONGOING PHASE 3 RANDOMIZED PRO-GLIO TRIAL
Authors: Heggebø L , Hellebust T , Hervani M , Henry T , Fjæra L , Evensen M , Gustafsson M , Sprauten M , Magelssen H , Blakstad H , Moorthy J , Andersson K , Rylander H , Goplen D , Brekke J , Johannessen T , Solheim T , Marienhagen K , Humberset Ø , Guldbjørnsen J , Bergström P , Agrup M , Kinhult S , Alkner S , Dahl L , Kristensen I , Gubanski M , Gojon H , Raunert I , Flejmer A , Jakobsson F , Ramberg C , Werlenius K , Blomstrand M , Brandal P 
Published: September 2023

Abstract

BACKGROUND
PRO-GLIO is an ongoing multicenter phase 3 randomized controlled trial in Norway and Sweden. In this trial, 224 adult patients with isocitrate dehydrogenase (IDH) -mutated diffuse gliomas grade 2-3, astrocytomas and oligodendrogliomas are randomized 1:1 between proton and photon radiotherapy. Study inclusion commenced in Oslo University Hospital (OUH) in January 2022, with other study-centers following. A number of outcomes will be assessed, including several survival, quality of life, and cognition parameters. For patients with diffuse gliomas delineation of target volumes when planning radiotherapy may be inherently difficult, not least due to the diffuse infiltrative growth pattern. There are also interobserver variability in delineation of organs at risk (OAR) and treatment planning. These factors may influence the planned and delivered treatment and thereby potentially affect clinical outcome. As part of the PRO-GLIO trial, all participating study-centers must undergo a qualifying radiotherapy dummy run procedure prior to initiation of patient inclusion to minimize the variations of these factors and to ensure protocol adherence.

MATERIAL AND METHODS
In the dummy run procedure, all centers delineate target volumes and OAR on a given case, and thereafter perform dose planning based on a consensus structure set for the same case. Swedish centers prepare photon and proton therapy plans, whereas Norwegian centers prepare photon plans only. Delineations are evaluated based on pre-defined quantitative and qualitative parameters. For all volumes - gross target volume (GTV), clinical target volume (CTV), and OARs - a Dice similarity coefficient (DSC) is calculated.

RESULTS
References values were made from consensus delineations among five radiation oncologists from OUH and Sahlgrenska University Hospital. For each of the target volumes and OARs, the DSC was cross calculated for the five experts, and the lowest value was used as a reference during the evaluation of submitted contours. Initial analysis has been performed based on data from the 6 centers which have completed the procedure. Mean DSC for GTV is 0.78, for CTV 0.87, for optic chiasm 0.42, for brain stem surface 0.92, and for right and left hippocampus 0.61 and 0.59, respectively. An inherent weakness of the DSC is that it is sensitive to the volume of the organ. This is seen in our data with the highest value for the largest volume (CTV) and a lower value for the optic chiasm. Thus, a qualitative evaluation was also performed. All submitted contours were approved.

CONCLUSION
The dummy run procedure revealed differences in OAR and target volume definition between centers and experts. Nonetheless, a DSC of 0.87 for CTV is re-assuring and prove a high coherence between participating centers. A dummy run procedure seems to be a valuable tool to ensure protocol adherence and draw attention to OAR and target volume delineation.