Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study
Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study
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DOI：
10.1016/j.radonc.2016.06.006
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发表时间：
2016-09-01
影响因子：
5.7
通讯作者：
Poetter, Richard
中科院分区：
文献类型：
--
作者：
Mazeron, Renaud.;Fokdal, Lars U.;Poetter, Richard
目的：在前瞻性研究中，建立同期放化疗和MRI引导的适应性近距离放射治疗(IBABT)宫颈癌患者晚期直肠发病率的剂量-体积-效应关系。材料和方法：所有患者均按机构方案进行治疗意向治疗。报告遵循GEC-ESTRO的建议(D-0.1cm3，D-2cm3)，采用等效剂量的生物效应模型(线性二次模型)(EQD2(3))。根据CTC-AE3.0对并发症进行评分。通过比较无事件期间的平均剂量、概率模型和对数等级检验来评估剂量-效应关系。结果：纳入960名患者。中位随访期为25.4个月。1级发生率为21.1%，2级为6.0%，3级为1.6%，4级为0.1%。D-ICRU、D-0.1cm3和D-2cm3的平均值分别为66.2±9.1Gy72.9+/-11.9Gy62.8+/-7.6Gy.剂量的增加与单个终点的严重程度和总体直肠并发症(1-4级)的增加相关(p<；0.001-0.026)，但狭窄除外(p=0.24-0.31)。概率模型显示D-2cm~3、D-0.1cm~3和DICRU与1~4级、2~4级和3~4级直肠事件发生的概率显著相关。总体直肠分级和Gt；=2的发病率为10%的等效D-2cm3为69.5Gy2(p<；0.0001)。根据6个D-2cm3水平对患者进行分类后，在大剂量亚组中观察到出血、直肠炎、瘘管和总体直肠发病率较差的结果。D-2cm3和Gt；=75Gy3年后发生瘘管的风险为12.5%，而低剂量组为0-2.7%(p>；0.001)。65GyD-2cm3和65Gy的直肠炎风险是65Gy的两倍。结论：晚期直肠发病率、总体和单个终点与剂量-体积(D-2cm3、D-0.1cm3)和剂量-点(D-ICRU)参数之间存在显著的相关性。D-2cm3=75Gy时，直肠疾病发生率更高，发病率更高。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Purpose: To establish dose volume-effect relationships predicting late rectal morbidity in cervix cancer patients treated with concomitant chemoradiation and MRI-guided adaptive brachytherapy (IBABT) within the prospective EMBRACE study.Material and method: All patients were treated with curative intent according to institutional protocols with chemoradiation and IGABT. Reporting followed the GEC-ESTRO recommendations (D-0.1cm3, D-2cm3), applying bioeffect modeling (linear quadratic model) with equieffective doses (EQD2(3)). Morbidity was scored according to the CTC-AE 3.0. Dose-effect relationships were assessed using comparisons of mean doses, the probit model and log rank tests on event-free periods.Results: 960 patients were included. The median follow-up was 25.4 months. Twenty point one percent of the patients had grade 1 events, 6.0% grade 2, 1.6% grade 3 and 0.1%, grade 4. The mean D-ICRU, D-0.1cm3 and D-2cm3 were respectively: 66.2 +/- 9.1 Gy, 72.9 +/- 11.9 Gy, and 62.8 +/- 7.6 Gy. Increase of dose was associated with increase in severity of single endpoints and overall rectal morbidity (grade 1-4) (p < 0.001-0.026), except for stenosis (p = 0.24-0.31). The probit model showed significant relationships between the D-2cm3, D-0.1cm3, and DICRU and the probability of grade 1-4, 2-4, and 3-4 rectal events. The equieffective D-2cm3 for a 10% probability for overall rectal grade >= 2 morbidity was 69.5 Gy (p < 0.0001). After sorting patients according to 6 D-2cm3 levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A D-2cm3 >= 75 Gy was associated with a 12.5% risk of fistula at 3 years versus 0-2.7% for lower doses (p > 0.001). A D-2cm3 < 65 Gy was associated with a two times lower risk of proctitis than D-2cm3 >= 65 Gy.Conclusions: Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose-volume (D-2cm3, D-0.1cm3) and dose-point (D-ICRU) parameters. A D-2cm3 = 75 Gy is associated with more major and more frequent rectal morbidity. (C) 2016 Elsevier Ireland Ltd. All rights reserved.