Impact of Patient Selection on Real-World Outcomes by Using the EMBRACE-II Treatment Protocol in Locally Advanced Cervical Cancer

Abstract

Purpose

External beam radiation therapy (EBRT), concomitant cisplatin, and magnetic resonance image guided adaptive brachytherapy performed according to the EMBRACE-II study protocol (IntErnational study on MRI-guided BRAchytherapy in locally advanced CErvical cancer) is considered state-of-the-art for the treatment of locally advanced cervical cancer. The aim of the present study was to evaluate the possibilities for realizing the planning aims and to assess the clinical outcome of using the EMBRACE-II treatment principles in real-world patients.

Methods and Materials

The EMBRACE-II treatment protocol was implemented in 2015 at Aarhus University Hospital as standard for all patients. The present analysis comprises a consecutive cohort treated from 2015 to 2019.

Results

In total 209 of 215 (97%) patients completed radiation therapy according to EMBRACE-II. Compared with 96 of 209 (46%) patients recruited in EMBRACE, major patient and disease related prognostic factors, were all significantly in disfavor for 113 of 209 (54%) patients treated according to EMBRACE-II, but not included in the trial. Nonetheless, the planning aims for EBRT and image guided adaptive brachytherapy were largely fulfilled in all patients. In contrast, the completion rate of 5 courses of concomitant cisplatin was reduced from 69% to 27% according to ± trial participation (P < .001) and was significantly influenced by age, comorbidity, performance status, and local tumor stage (P < .001). Overall 5-year local control was high (89%) and the rate of severe radiation-related side effects was low (7%). Advanced local tumor stage was a negative prognostic factor for loco-regional control, systemic control, and survival (P < .001), whereas concomitant cisplatin was important for EBRT-target control (P < .002).

Conclusions

The dose-volume planning aims derived from EMBRACE-II for combining EBRT and brachytherapy are achievable in real-world patients while delivery of concomitant cisplatin is challenging. The use of carboplatin or increasing the dose of EBRT in patients unfit for concomitant cisplatin may be relevant for adjusting EMBRACE-II to the real world. In addition, wider indications for elective paraortic EBRT may be appropriate for patients with large primary tumors, irrespective of nodal status.