TY - JOUR
T1 - Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis
AU - Spampinato, Sofia
AU - Fokdal, Lars U.
AU - Pötter, Richard
AU - Haie-Meder, Christine
AU - Lindegaard, Jacob C.
AU - Schmid, Maximilian P.
AU - Sturdza, Alina
AU - Jürgenliemk-Schulz, Ina M.
AU - Mahantshetty, Umesh
AU - Segedin, Barbara
AU - Bruheim, Kjersti
AU - Hoskin, Peter
AU - Rai, Bhavana
AU - Huang, Fleur
AU - Cooper, Rachel
AU - van der Steen-Banasik, Elzbieta
AU - van Limbergen, Erik
AU - Sundset, Marit
AU - Westerveld, Henrike
AU - Nout, Remi A.
AU - Jensen, Nina B. K.
AU - Kirisits, Christian
AU - Kirchheiner, Kathrin
AU - Tanderup, Kari
N1 - Funding Information: The EMBRACE study was supported by Elekta AB and Varian Medical System through unrestricted research grants and study sponsoring through the Medical University of Vienna. The work of this manuscript was supported via grants from the Danish Cancer Society ( R101-A685414-S31 , R150-A10177-001 , R146-A9459-16-S2 ). Publisher Copyright: © 2021 Elsevier B.V.
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Material and methods: Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC “very much” and “quite a bit” or worse. Results: Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3–120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for ”quite a bit” or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain “quite a bit” or worse. An increase from 75 Gy to 80 Gy in bladder D2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis. Conclusion: Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose–effect was established with bladder D2cm3, reinforcing the importance of continued optimization during individualized IGABT planning.
AB - Purpose: To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Material and methods: Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC “very much” and “quite a bit” or worse. Results: Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3–120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for ”quite a bit” or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain “quite a bit” or worse. An increase from 75 Gy to 80 Gy in bladder D2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis. Conclusion: Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose–effect was established with bladder D2cm3, reinforcing the importance of continued optimization during individualized IGABT planning.
KW - Cervical cancer
KW - Clinical study
KW - Dose-effect relationship
KW - IGABT
KW - Risk factors
KW - Urinary morbidity
UR - http://www.scopus.com/inward/record.url?scp=85101119760&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.radonc.2021.01.019
DO - https://doi.org/10.1016/j.radonc.2021.01.019
M3 - Article
C2 - 33545254
SN - 0167-8140
VL - 158
SP - 312
EP - 320
JO - Radiotherapy and oncology
JF - Radiotherapy and oncology
ER -