1. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study
- Author
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Melissa Christiaens, Marisol De Brabandere, Taran Paulsen Hellebust, Janaki Hadjiev, Alina Sturdza, Ina M. Jürgenliemk-Schulz, Israel Fortin, Søren M. Bentzen, Kari Tanderup, Umesh Mahantshetty, Stefan Ecker, Deidre Batchelar, Stéphanie Smet, Kathrin Kirchheiner, Fleur Huang, Kenji Yoshida, Katarina Majercakova, Yusung Kim, Petra Georg, Anne Beate Langeland Marthinsen, Johannes Dimopoulos, Neamat Hegazy, Petra Trnkova, Arun S Oinam, Bernard Oosterveld, Primoz Petric, Beth Erickson, Gerry Lowe, Itxa Mora, Mario Federico, Jan-Erik Palmgren, Ludy C.H.W. Lutgens, Marianne S. Assenholt, Margit Valgma, Elzbieta van der Steen-Banasik, Karen S. Nkiwane, Kjersti Bruheim, Henrike Westerveld, Elena Fidarova, Bradley R. Pieters, Christian Kirisits, Richard Pötter, Lars Fokdal, Ian Dilworth, Susovan Banerjee, Marit Sundset, Robert Hudej, Geraldine Jacobson, Erik Van Limbergen, Maarit Anttila, Thomas Liederer, Isabelle Dumas, Elke Dörr, Pittaya Dankulchai, L.T. Tan, Jusheng An, Barbara Segedin, Jason Rownd, Christine Haie-Meder, Diane Whitney, Francois Bachand, Noha Jastaniyah, Martijn Ketelaars, Rachel Cooper, Peter Hoskin, Monica Serban, E. Villafranca, Nicole Nesvacil, Astrid de Leeuw, Hilde Janssen, Jacob Christian Lindegaard, Dina Najjari Jamal, Kees Koedooder, Cyrus Chargari, Maximilian Schmid, Gergely Antal, Thomas Berger, Robin Ristl, Remi A. Nout, Nina Boje Kibsgaard Jensen, Brigitte Reinniers, Tamara Diendorfer, Geetha Menon, Sofia Spampinato, Dragan Misimovic, Joyce Siu Yu Wong, Laura Motisi, Anders Schwartz-Vittrup, Bhavana Rai, Joanna Gora, Jamema Swamidas, Peter Bownes, University of Zurich, Schmid, Maximilian Paul, Radiotherapy, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and Quality of Life
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Brachytherapy ,Uterine Cervical Neoplasms ,610 Medicine & health ,Disease-Free Survival ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Stage (cooking) ,Prospective cohort study ,Aged ,Cervical cancer ,business.industry ,Chemoradiotherapy ,medicine.disease ,Magnetic Resonance Imaging ,10044 Clinic for Radiation Oncology ,Clinical trial ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,2730 Oncology ,Radiology ,Cisplatin ,business ,Cohort study ,Radiotherapy, Image-Guided - Abstract
Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems.
- Published
- 2021