Kirchheiner Kathrin, Nout Remi A, Lindegaard Jacob C, Haie-Meder Christine, Mahantshetty Umesh, Segedin Barbara, Jürgenliemk-Schulz Ina M, Hoskin Peter J, Rai Bhavana, Dörr Wolfgang, Kirisits Christian, Bentzen Søren M, Pötter Richard, Tanderup Kari
Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Austria.
Department of Radiation Oncology, Leiden University Medical Center, The Netherlands.
Radiother Oncol. 2016 Jan;118(1):160-6. doi: 10.1016/j.radonc.2015.12.025. Epub 2016 Jan 9.
BACKGROUND/PURPOSE: To identify risk factors for vaginal stenosis and to establish a dose-effect relationship for image-guided brachytherapy in locally advanced cervical cancer.
MATERIALS/METHODS: Patients 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.
In 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 >45 Gy/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 65 Gy, 27% at 75 Gy and 34% at 85 Gy (recto-vaginal reference point dose).
Keeping the EBRT dose at 45 Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65 Gy EQD2 (EBRT+brachytherapy dose) to the recto-vaginal reference point is therefore proposed.
背景/目的：确定阴道狭窄的危险因素，并建立局部晚期宫颈癌影像引导近距离放疗的剂量效应关系。
材料/方法：选取正在进行的EMBRACE研究中的患者，这些患者在基线和至少一次随访时进行了前瞻性发病率评估（CTCAEv3.0）。在单变量和多变量分析（Cox比例风险模型）中，对患者、疾病和治疗特征作为阴道狭窄G⩾2的危险因素进行测试，并从估计值中推导出剂量效应曲线。使用ICRU直肠点来得出直肠-阴道参考点剂量。
纳入630例患者（中位随访24个月），阴道狭窄G⩾2的2年精算估计值为21%。直肠-阴道参考点剂量（HR=1.025，p=0.029）、外照射放疗（EBRT）剂量>45 Gy/25分次（HR=1.770，p=0.056）以及肿瘤侵犯阴道（HR=2.259，p⩽0.001）是阴道狭窄的危险因素，已对中心报告效应进行校正。根据模型曲线，直肠-阴道参考点剂量在65 Gy时风险为20%，75 Gy时为27%，85 Gy时为34%。
将EBRT剂量保持在45 Gy/25分次，并减少近距离放疗对阴道的剂量贡献，可降低狭窄风险。因此，建议直肠-阴道参考点的等效剂量2（EBRT+近距离放疗剂量）的计划目标⩽65 Gy。
