Dose–effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study

Publication date: Available online 9 January 2016
Source:Radiotherapy and Oncology
Author(s): Kathrin Kirchheiner, Remi A. Nout, Jacob C. Lindegaard, Christine Haie-Meder, Umesh Mahantshetty, Barbara Segedin, Ina M. Jürgenliemk-Schulz, Peter J. Hoskin, Bhavana Rai, Wolfgang Dörr, Christian Kirisits, Søren M. Bentzen, Richard Pötter, Kari Tanderup
Background/purposeTo identify risk factors for vaginal stenosis and to establish a dose–effect relationship for image-guided brachytherapy in locally advanced cervical cancer.Materials/MethodsPatients from the ongoing EMBRACE study with prospectively assessed morbidity (CTCAEv3.0) at baseline and at least one follow-up were selected. Patient-, disease- and treatment characteristics were tested as risk factors for vaginal stenosis G⩾2 in univariate and multivariable analyses (Cox proportional hazards model) and a dose–effect curve was deduced from the estimates. The ICRU rectum point was used to derive the recto-vaginal reference point dose.ResultsIn 630 patients included (median follow-up 24months), 2-year actuarial estimate for vaginal stenosis G⩾2 was 21%. Recto-vaginal reference point dose (HR=1.025, p=0.029), external beam radiotherapy (EBRT) dose >45Gy/25 fractions (HR=1.770, p=0.056) and tumor extension in the vagina (HR=2.259, p⩽0.001) were risk factors for vaginal stenosis, adjusted for center reporting effects. Based on the model curve, the risk was 20% at 65Gy, 27% at 75Gy and 34% at 85Gy (recto-vaginal reference point dose).ConclusionKeeping the EBRT dose at 45Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65Gy EQD2 (EBRT+brachytherapy dose) to the recto-vaginal reference point is therefore proposed.



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