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

M. Serban; S. Spampinato; A. de Leeuw; I. Fortin; C. Kirisits; X. Y. Ye; M. Schmid; P. Hoskin; U. Mahantshetty; B. Segedin; K. Bruheim; F. Huang; R. Bhavana; R. Cooper; Van Der Steen Banasik e; E. Van Limbergen; B. R. Pieters; L. T. Tan; S. Chopra; R. Nout; N. Nesvacil; K. Kirchheiner; R. Pötter; I. M. Jürgenliemk-Schulz; K. Tanderup

doi:10.1016/j.radonc.2025.110954

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

M. Serban^*
, S. Spampinato
, A. de Leeuw
, I. Fortin
, C. Kirisits
, X. Y. Ye
, M. Schmid
, P. Hoskin
, U. Mahantshetty
, B. Segedin
, K. Bruheim
, F. Huang
, R. Bhavana
, R. Cooper
, Van Der Steen Banasik e
, E. Van Limbergen
, B. R. Pieters
, L. T. Tan
, S. Chopra
, R. Nout

N. Nesvacil, K. Kirchheiner, R. Pötter, I. M. Jürgenliemk-Schulz, K. Tanderup

^*Corresponding author for this work

Princess Margaret Hospital Cancer Centre
University of Toronto
Aarhus University
Erasmus MC Cancer Institute
Utrecht University
University of Montreal
Medical University of Vienna
University Health Network (Toronto)
Cancer Center, Mount Vernon Hospital, London, UK
Tata Memorial Hospital
University of Ljubljana
University of Oslo
Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Canada
Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Leeds Teaching Hospitals NHS Trust
Department of Radiotherapy, Radiotherapiegroep Arnhem, The Netherlands
KU Leuven
Amsterdam UMC - University of Amsterdam
Amsterdam UMC
Cambridge University Hospitals NHS Foundation Trust
Homi Bhabha National Institute

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	110954
Journal	Radiotherapy and oncology
Volume	210
DOIs	https://doi.org/10.1016/j.radonc.2025.110954
Publication status	Published - 1 Sept 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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Evaluation-of-brachytherapy-applicators-and-their-association-with-morbidity-and-local-control-in-cervix-cancer.pdfFinal published version, 2.09 MBLicence: Taverne

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Serban, M., Spampinato, S., de Leeuw, A., Fortin, I., Kirisits, C., Ye, X. Y., Schmid, M., Hoskin, P., Mahantshetty, U., Segedin, B., Bruheim, K., Huang, F., Bhavana, R., Cooper, R., Steen Banasik e, V. D., Limbergen, E. V., Pieters, B. R., Tan, L. T., Chopra, S., ... Tanderup, K. (2025). Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis. Radiotherapy and oncology, 210, Article 110954. https://doi.org/10.1016/j.radonc.2025.110954

@article{b7ed869886ec4db68b5c9b0944f4988f,

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

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",

author = "M. Serban and S. Spampinato and \{de Leeuw\}, A. and I. Fortin and C. Kirisits and Ye, \{X. Y.\} and M. Schmid and P. Hoskin and U. Mahantshetty and B. Segedin and K. Bruheim and F. Huang and R. Bhavana and R. Cooper and \{Steen Banasik e\}, \{Van Der\} and Limbergen, \{E. Van\} and Pieters, \{B. R.\} and Tan, \{L. T.\} and S. Chopra and R. Nout and N. Nesvacil and K. Kirchheiner and R. P{\"o}tter and J{\"u}rgenliemk-Schulz, \{I. M.\} and K. Tanderup",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier B.V.",

year = "2025",

month = sep,

day = "1",

doi = "10.1016/j.radonc.2025.110954",

language = "English",

volume = "210",

journal = "Radiotherapy and oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

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Serban, M, Spampinato, S, de Leeuw, A, Fortin, I, Kirisits, C, Ye, XY, Schmid, M, Hoskin, P, Mahantshetty, U, Segedin, B, Bruheim, K, Huang, F, Bhavana, R, Cooper, R, Steen Banasik e, VD, Limbergen, EV, Pieters, BR, Tan, LT, Chopra, S, Nout, R, Nesvacil, N, Kirchheiner, K, Pötter, R, Jürgenliemk-Schulz, IM & Tanderup, K 2025, 'Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis', Radiotherapy and oncology, vol. 210, 110954. https://doi.org/10.1016/j.radonc.2025.110954

TY - JOUR

T1 - Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer

T2 - An EMBRACE I analysis

AU - Serban, M.

AU - Spampinato, S.

AU - de Leeuw, A.

AU - Fortin, I.

AU - Kirisits, C.

AU - Ye, X. Y.

AU - Schmid, M.

AU - Hoskin, P.

AU - Mahantshetty, U.

AU - Segedin, B.

AU - Bruheim, K.

AU - Huang, F.

AU - Bhavana, R.

AU - Cooper, R.

AU - Steen Banasik e, Van Der

AU - Limbergen, E. Van

AU - Pieters, B. R.

AU - Tan, L. T.

AU - Chopra, S.

AU - Nout, R.

AU - Nesvacil, N.

AU - Kirchheiner, K.

AU - Pötter, R.

AU - Jürgenliemk-Schulz, I. M.

AU - Tanderup, K.

PY - 2025/9/1

Y1 - 2025/9/1

N2 - 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.

AB - 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.

KW - Brachytherapy applicators

KW - Cervical cancer

KW - EMBRACE study

KW - Local control outcomes

KW - MR-guided brachytherapy

KW - Morbidity outcomes

KW - Tandem and Ovoids

KW - Tandem and Ring

UR - https://www.scopus.com/pages/publications/105011975966

U2 - 10.1016/j.radonc.2025.110954

DO - 10.1016/j.radonc.2025.110954

M3 - Article

C2 - 40449684

SN - 0167-8140

VL - 210

JO - Radiotherapy and oncology

JF - Radiotherapy and oncology

M1 - 110954

ER -

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

Abstract

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Keywords

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