Authors: Pötter|, Richard(1)*[richard.poetter@akhwien.at];Tanderup|, Kari(2);Schmid|, Maximilian(1);Haie-Meder|, Christine(3);Fokdal|, Lars U.(2);Sturdza|, Alina(1);Hoskin|, Peter(4);Mahantshetty|, Umesh(5);Segedin|, Barbara(6);Bruheim|, Kjersti(7);Huang|, Fleur(8);Rai|, Bhavana (9);Cooper|, Rachel (10);van der Steen-Banasik|, Elzbieta(11);van Limbergen|, Erik(12);Pieters|, Bradley(13);Tan|, Li Tee(14);Nout|, Remi(15);de Leeuw|, Astrid C.(16);Nesvacil|, Nicole(1);Kirchheiner|, Kathrin(1);Jürgenliemk-Schulz|, Ina(16);Kirisits|, Christian(1);Lindegaard|, Jacob C.(2);Embrace|, Collaborative Group(17);
(1)Medical University Vienna, Department of Radiation Oncology, Vienna, Austria;(2)Aarhus University Hospital, Department of Oncology, Aarhus, Denmark;(3)Gustave-Roussy, Department of Radiotherapy, Villejuif, France;(4)Mount Vernon Hospital, Mount Vernon Cancer Centre, Northwood, United Kingdom;(5)Tata Memorial Hospital, Department of Radiation Oncology, Mumbai, India;(6)Institute of Oncology Ljubljana, Department of Radiotherapy, Ljubljana, Slovenia;(7)The Norwegian Radium Hospital- Oslo University Hospital, Department of Oncology, Oslo, Norway;(8)Cross Cancer Institute and University of Alberta, Department of Oncology, Edmonton, Canada;(9)Postgraduate Institute of Medical Education and Research, Department of Radiotherapy and Oncology, Chandigarh, India;(10)St James's University Hospital, Leeds Cancer Centre, Leeds, United Kingdom;(11)Radiotherapiegroep Arnhem, Department of Radiotherapy, Arnhem, The Netherlands;(12)UZ Leuven, Department of Radiation Oncology, Leuven, Belgium;(13)Amsterdam UMC- Academic Medical Center- University of Amsterdam, Department of Radiation Oncology, Amsterdam, The Netherlands;(14)Addenbrooke´s Hospital- Cambridge University Hospitals, Department of Oncology, Cambridge, United Kingdom;(15)Leiden University Medical Center, Department of Radiation Oncology, Leiden, The Netherlands;(16)University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands;(17)EMBRACE Collaborative Group, EMBRACE Collaborative Group, EMBRACE Collaborative Group, Austria;
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Purpose or Objective
To present mature overall clinical results from the prospective observational multi-centre IntErnational study on MRI-guided BRAchytherapy in locally advanced CErvical Cancer (EMBRACE).
Material and Methods
Data from 1416 pts with locally advanced cervical cancer (LACC) stage IB-IVA and IVB (in paraaortic nodes (PAN)) treated 2008-2015 in 23 centres were prospectively collected. Treatment comprised definitive EBRT (3DCRT or IMRT) and concurrent cisplatin followed by MR image guided adaptive brachytherapy (IGABT) based on MRI with applicator in situ. IGABT targets, OAR and dose volume parameters were reported following GEC-ESTRO recommendations (2005). EBRT dose was 45-50Gy (1.5-2.0Gy/fraction). IGABT doses were prescribed according to institutional guidelines. A comprehensive QA programme was applied. Actuarial (Kaplan–Meier) estimates for the first recurrence/vital status (before 15/07/2019) were calculated at 3/5 years for local control (LC), pelvic control (PC), disease control (DC, any recurrence), overall survival (OS) and disease-free survival (DFS, any recurrence or death). Toxicity was prospectively assessed (CTCAEv3.0).
Results
Median follow up was 51 months for 1318 pats (98 pts excluded: incorrect selection, no data, no follow up). FIGO2009 stage distribution was IB 241 (18%) (IB2 118), IIA 67 (5%), IIB 683 (52%), IIIA 13 (1%), IIIB 183 (14%), IVA 34 (3%), IVB 97 (7%). 686 (52%) were node-positive (N+). 1080 (82%) had squamous Ca, 188 (14%) adeno, 49 (4%) adenosquamous. Mean EBRT dose was 46±2Gy. 95% received cisplatin. IGABT technique was intracavitary (IC) in 57% and IC/interstitial (IS) in 43%. Mean CTVHR volume was 33±19 cm3. Mean CTVHR D90% was 89±9Gy10, for stage IIIB 87±8 Gy10, IVA 83±10Gy10. Mean D2cm³ for bladder was 76±10Gy3, rectum 63±7Gy3, sigmoid 64±7Gy3, bowel 63±10Gy3, rectovaginal point 66±9Gy3. Overall 331 pts had recurrence (multiple events possible) - local 98, pelvic lymph nodes 89 (overall pelvis 164), PAN 106. 184 pts had recurrence beyond PAN. At the time of analysis, 363 pts had died, 281 from disease progression. At 5 years, LC was 92%, PC 87%, DC 74%, OS 74%, DFS 68% (table 1a, figure 1). For IIIB disease, 5-year LC was 91%, PC 85%, OS 64%, for IVA LC was 91%, PC 81%, OS 52%. 3/5-year OS was 87/81% for N- pts and 76/67% for N+ pts. Crude G3-5 morbidity at 5 years was genito-urinary 6.5% (n=81), gastro-intestinal 7.6% (n=95), vagina 6.1% (n=76).
Conclusion
MRI-based IGABT in combination with chemo-RT results in excellent and stable long-term local, pelvic, disease control and survival across all stages with limited serious morbidity. These results compare overall favourably with RetroEMBRACE, especially for advanced disease (compare table 1a and 1b) and should be used as the benchmark for routine clinical practice as well as for design of future clinical trials. The results will also provide the frame for further EMBRACE related analyses.