The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies Richard Pötter,

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The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies Richard Pötter, Kari Tanderup, Christian Kirisits, Astrid de Leeuw, Kathrin Kirchheiner, Remi Nout, Li Tee Tan, Christine Haie-Meder, Umesh Mahantshetty, Barbara Segedin, Peter Hoskin, Kjersti Bruheim, Bhavana Rai, Fleur Huang, Erik Van Limbergen, Max Schmid, Nicole Nesvacil, Alina Sturdza, Lars Fokdal, Nina Boje Kibsgaard Jensen, Dietmar Georg, Marianne Assenholt, Yvette Seppenwoolde, Christel Nomden, Israel Fortin, Supriya Chopra, Uulke van der Heide, Tamara Rumpold, Jacob Christian Lindegaard, Ina Jürgenliemk- Schulz Clinical and Translational Radiation Oncology Volume 9, Pages 48-60 (February 2018) DOI: 10.1016/j.ctro.2018.01.001 Copyright © 2018 The Authors Terms and Conditions

Clinical and Translational Radiation Oncology 2018 9, 48-60DOI: (10 Clinical and Translational Radiation Oncology 2018 9, 48-60DOI: (10.1016/j.ctro.2018.01.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 1 The figure demonstrates the principles for dose de-escalation and dose escalation in EMBRACE II. The current distribution of CTVHR dose and volume in the EMBRACE study is shown (each point represents one patient). A number of 6 dose and volume groups are defined according to cut-points of 85 Gy and 95 Gy for the adaptive CTVHR D90 and of 30 cm3 for the CTVHR volume. For each dose-volume group the expected actuarial local control at 3 years is indicated, according to dose-effect data from the retroEMBRACE study [33]. Clinical and Translational Radiation Oncology 2018 9, 48-60DOI: (10.1016/j.ctro.2018.01.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 2 Schematic diagram for EBRT and brachytherapy targets in cervical cancer, stage IIB bulky disease and good response after chemo-radiotherapy: coronal, transversal and sagittal view. For further details see figure 3.3 and 9.6 in the EMBRACE II protocol adapted from figure 5.10 from ICRU report 89 [9]. Panel A: EBRT targets: large GTV-Tinit, initial CTV-THR, and initial CTV-TLR. Panel B: Brachytherapy targets: limited GTV-Tres (residual GTV), adaptive CTV-THR, and CTV-TIR (GTV-Tinit plus margins around the CTV-THR). Maximum width, thickness and height of the adaptive CTV-THR are indicated. Clinical and Translational Radiation Oncology 2018 9, 48-60DOI: (10.1016/j.ctro.2018.01.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 3 Schematic Diagram for lymph node elective CTVs based on risk of lymphatic spread, “Small Pelvis”, “Large Pelvis”, “Large Pelvis + para-aortic”. The risk groups are defined in . Clinical and Translational Radiation Oncology 2018 9, 48-60DOI: (10.1016/j.ctro.2018.01.001) Copyright © 2018 The Authors Terms and Conditions