Research in context
Evidence before this study
We searched PubMed for reports published in English between Jan 1, 2000, and June 1, 2020, using the search terms “image guided adaptive brachytherapy” (IGABT), “MRI”, “cervical cancer”, “local control”, “overall survival”, and “prospective clinical study”. No study fulfilling these criteria was identified. The clinical evidence so far is based on several retrospective patient cohort studies pointing to improvement of local control and reduction of severe morbidity by IGABT in locally advanced cervical cancer, with only few variations in treatment and outcomes. Additionally, international recommendations have been published on the concept and reporting of IGABT (Groupe Européen de Curiethérapie European Society for Radiation Oncology [GEC ESTRO] recommendations, International Commission of Radiation Units report 89).
Added value of this study
To our knowledge, EMBRACE-I is the first prospective multi-institutional observational cohort study using MRI-based IGABT in addition to concurrent chemoradiotherapy in locally advanced cervical cancer, showing the clinical feasibility of the combined treatment. Effective dose coverage could be reached in the target while sparing organs at risk through adjustment of IGABT application technique (intracavitary and interstitial needles) and multiparametric three dimensional treatment planning. EMBRACE-I provides mature and high-quality clinical outcome data showing a high rate of local control across all stages greater than ever reported before. This improvement was associated with a high rate of pelvic control and overall survival. Severe late morbidity (eg, grade ≥3) was limited per organ site and endpoint.
Implications of all the available evidence
The results of EMBRACE-I provide the clinical evidence for MRI-guided IGABT as being the new gold-standard IGABT of locally advanced cervical cancer to be implemented across the world, replacing the traditional two dimensional point A concept. EMBRACE-I entails a comprehensive system for collecting information on patient, tumour, and treatment parameters, associating these with disease outcome and morbidity, and quality of life. The high level of local and pelvic control with limited severe morbidity and favourable overall survival will serve as a platform for future studies focusing on nodal and systemic control, which are the barriers for improved disease control and survival. IGABT, as practiced in EMBRACE-I, has become the new standard of care in Europe according to the recommendations of the European Society of Gynaecologic Oncology, the European Society for Radiotherapy and Oncology, and the European Society of Pathology. Findings from EMBRACE-I were the basis for the ongoing interventional prospective multicenter EMBRACE-II (NCT 03617133) study, in which specific planning aims and dose-volume constraints are enforced. The EMBRACE I results are also being increasingly used as a reference in many centres worldwide and in clinical studies reflecting clinical, biological, and technical parameters of importance for further optimising the therapeutic ratio for chemoradiotherapy and IGABT in locally advanced cervical cancer.