Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image–Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study
Authors: Schmid Maximilian P. , Lindegaard Jacob C. , Mahantshetty Umesh , Tanderup Kari , Jürgenliemk-Schulz Ina , Haie-Meder Christine , Fokdal Lars U. , Sturdza Alina , Hoskin Peter , Segedin Barbara , Bruheim Kjersti , Huang Fleur , Rai Bhavana , Cooper Rachel , van der Steen-Banasik Elzbieta , Van Limbergen Erik , Pieters Bradley R. , Petric Primoz , Ramazanova Dariga , Ristl Robin , Kannan Sadhana , Hawaldar Rohini , Ecker Stefan , Kirchheiner Kathrin , Tan Li Tee , Nout Remi , Nesvacil Nicole , de Leeuw Astrid , Pötter Richard , Kirisits Christian ,   for the EMBRACE Collaborative Group, Jurgenliemk-Schulz Ina Maria , Huang Fleur , Christiaens Melissa , Janssen Hilde , Sundset Marit , Lutgens Ludy C.H.W. , Villafranca Elena , Hadjiev Janaki , Bachand Francois , Erickson Beth , Jacobson Geraldine , Anttila Maarit , Dumas Isabelle , Lowe Gerry , Swamidas Jamema , Hudej Robert , Hellebust Taran Paulsen , Menon Geetha , Oinam Arun S. , Bownes Peter , De Brabandere Marisol , Oosterveld Bernard , Koedooder Kees , Langeland Marthinsen Anne Beate , Whitney Diane , Ketelaars Martijn , Reiniers Brigitte , Mora Itxa , Antal Gergely , Batchelar Deidre , Rownd Jason , Kim Yusung , Palmgren Jan-Erik , Mazeron Renaud , Chargari Cyrus , Spampinato Sofia 
Published: January 2023

PURPOSE To report clinical and treatment characteristics, remission and failure patterns, and risk factors for local failure (LF) from the EMBRACE-I study. MATERIALS AND METHODS EMBRACE-I was a prospective, observational, multicenter cohort study on magnetic resonance imaging–based image-guided adaptive brachytherapy (MR-IGABT) in locally advanced cervical cancer. Treatment consisted of external beam radiotherapy, concurrent chemotherapy, and MR-IGABT. LF was defined as progressive or recurrent disease in the cervix, uterus, parametria, pelvic wall, or vagina. Competing risk analysis was used to estimate local tumor control (LC) and Cox proportional regression models for multivariable analysis and dose-response analysis. RESULTS One thousand three hundred eighteen patients with a median follow-up of 52 months were available for this analysis. Eighty-one patients had persistent disease 3 months after end of treatment. Of those, 60 patients achieved LC at 6-9 months without further treatment, whereas 21 patients had progressive disease. In addition, 77 patients developed a local recurrence after complete remission comprising a total number of 98 LFs. LFs were located inside the MR-IGABT target volumes in 90% of patients with LF. In multivariable analysis, histology, minimal dose to 90% of high-risk clinical target volume (CTVHR), maximum tumor dimension, CTVHR > 45 cm3, overall treatment time, tumor necrosis on magnetic resonance imaging at diagnosis, uterine corpus infiltration at diagnosis and at MR-IGABT, and mesorectal infiltration at MR-IGABT had significant impact on LF. Dose-response analysis showed that a minimal dose to 90% of 85 Gy to the CTVHR led to 95% (95% CI, 94 to 97) LC 3 years postintervention for squamous cell in comparison to 86% (95% CI, 81 to 90) for adeno/adenosquamous carcinoma histology. CONCLUSION The present study demonstrates the safety and validity of the GYN GEC-ESTRO/ICRU-89 target concept and provides large-scale evidence for dose prescription and new risk factors for LF in MR-IGABT in locally advanced cervical cancer.