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Multicenter Study
. 2025 Sep:210:110954.
doi: 10.1016/j.radonc.2025.110954. Epub 2025 May 29.

Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis

M Serban  1 , S Spampinato  2 , A de Leeuw  3 , I Fortin  4 , C Kirisits  5 , X Y Ye  6 , M Schmid  5 , P Hoskin  7 , U Mahantshetty  8 , B Segedin  9 , K Bruheim  10 , F Huang  11 , R Bhavana  12 , R Cooper  13 , Van Der Steen Banasik E  14 , E Van Limbergen  15 , B R Pieters  16 , L T Tan  17 , S Chopra  18 , R Nout  19 , N Nesvacil  5 , K Kirchheiner  5 , R Pötter  5 , I M Jürgenliemk-Schulz  3 , K Tanderup  20
Affiliations
Multicenter Study

Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis

M Serban et al. Radiother Oncol. 2025 Sep.

Abstract

Purpose: To investigate the effects of brachytherapy (BT) applicator and implant type on morbidity and local control (LC) in locally advanced cervix cancer patients.

Methods: 1071 patients treated with radiochemotherapy including MRI-guided BT using tandem&ring (T&R) or tandem&ovoids (T&O) from 19 EMBRACE-I centers were analyzed. Intracavitary (IC) or intracavitary/interstitial (IC/IS) implants were used. Centers came from different brachytherapy traditions and followed their institutional dose aims and planning strategies. LC and physician-assessed morbidity (median follow-up 48 months) was compared between applicator/implant types using Cox proportional hazard model adjusting for patient characteristics and treatment-related potential confounders. Moderate-to-severe (G ≥ 2) genito-urinary (cystitis/frequency/incontinence), gastro-intestinal (proctitis/bleeding/diarrhea) and vaginal (stenosis/mucositis) symptoms were analysed individually. Severe events (G ≥ 3) were pooled per organ.

Results: The T&O (n = 346) compared to T&R (n = 725) had a higher risk of morbidity, with HRs > 1.3 in 14/16 individual G ≥ 2 symptoms and in 3/4 G ≥ 3 pooled organ symptoms. Patients treated with IC/IS (n = 512) compared to IC (n = 559) were not at higher risk of G ≥ 2 symptoms, with HRs < 1 in 6/8 MVAs. Crude incidence of local failure was 7.3 % (25/343) for T&O and 6.6 % (47/712) for T&R.

Conclusions: In this patient cohort, treated between 2008-2015, T&R and T&O demonstrated comparable LC. However, a higher risk of morbidity is reported for T&O. This increased risk was partly explained by hotspot doses, with factors such as irradiated volumes and organ irradiation length also contributing. Additionally, implant quality, dose planning aims and strategies, and morbidity reporting may have impacted the observed differences in morbidity. IC/IS applicators did not increase morbidity risk compared to IC applicators.

Keywords: Brachytherapy applicators; Cervical cancer; EMBRACE study; Local control outcomes; MR-guided brachytherapy; Morbidity outcomes; Tandem and Ovoids; Tandem and Ring.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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