宫颈癌内外照射后放射性直肠损伤临床预测模型的研究

目的 探讨宫颈癌内外照射放疗不同剂量叠加方式的剂量学差异,建立宫颈癌放疗后慢性放射性直肠损伤(RLRI)的临床预测模型。方法 回顾性分析2020年1月1日至2021年11月30日于川北医学院附属医院肿瘤科接受根治性同步放化疗宫颈癌患者的临床资料,放疗采用外照射+近距离治疗方式,内外照射剂量评估采用内、外照射生物等效剂量(EQD2)参数直接叠加和内外照射三维计划图像形变配准(DIR)剂量叠加,分析两种剂量评估方式剂量学差异。RLRI分级标准采用肿瘤放射治疗协作组标准。运用两种剂量评估方式构建RLRI的预测模型,使用受试者工作特征(ROC)曲线计算曲线下面积,以评估不同剂量评估方式的预测准确性。结果 多次近距离治疗剂量叠加的EQD2参数较DIR剂量叠加高危临床靶区D_95%和D_90%分别高2.18和2.92 Gy,直肠D_{2 cm³}、D_{1 cm³}、D_{0.1 cm³}分别高1.74、2.28、2.26 Gy(t=3.82、5.21、4.58、5.17、2.05,P<0.05)。外照射与近距离治疗,直肠D_{2 cm³}、D_{1 cm³}、D_{0.1 cm³}的EQD2参数直接叠加比DIR剂量叠加高6.22、7.61、9.56 Gy(t=9.40、10.59、7.87,P<0.001)。联合预测模型ROC曲线下面积为0.788,最佳预测阈值的灵敏度为0.850,特异度为0.660,Hosmer-Lemeshow拟合优度检验显示,拟合优度较好(P>0.05)。传统预测指标DIR剂量叠加的预测模型:直肠D_{2 cm³}、D_{1 cm³}的ROC曲线下面积分别为0.784、0.763,最佳预测阈值的灵敏度分别为0.850、0.750,特异度分别为0.679、0.717。结论 内外照射EQD2参数直接叠加与三维计划图进行DIR剂量叠加评估剂量参数有剂量学差异。DIR剂量叠加直肠D_{2 cm³}、D_{1 cm³}与联合预测模型预测RLRI的价值较高,但联合预测模型预测RLRI计算复杂,建议临床上通过DIR剂量叠加直肠D_{2 cm³}、D_{1 cm³}预测RLRI。

Clinical prediction models of radiation-induced rectal injury after brachytherapy combined with external beam radiation therapy for cervical cancer

Objective To explore the dosimetric differences of different dose accumulation method for brachytherapy combined with external beam radiation therapy (EBRT) of cervical cancer and establish clinical prediction models for radiation-induced late rectal injury (RLRI) after radiotherapy. Methods A retrospective analysis was conducted for the clinical data of patients who received radical concurrent chemoradiotherapy (CCRT) for cervical cancer in the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College from January 1, 2020 to November 30, 2021. EBRT combined with brachytherapy was employed for the patients, and dose assessment was performed in two means: the direct accumulation using equivalent dose in 2-Gy fractions (EQD2) and deformable image registration (DIR)-based dose accumulation of 3D planning images. The toxicity criteria of the Radiation Therapy Oncology Group were adopted as the RLRI grading criteria. The prediction models of RLRI using both dose assessment method were constructed. The areas under the receiver operating characteristic (ROC) curves were calculated to assess the predictive accuracy of the different dose assessment method. Results In the case of brachytherapy, the D_95% and D_90% EQD2 doses to high-risk clinical target volumes (HR-CTVs) were 2.18 and 2.92 Gy higher respectively and the D_{2 cm³}, D_{1 cm³}, and D_{0.1 cm³} EQD2 doses to the rectal were 1.74, 2.28, and 2.26 Gy higher, respectively compared to DIR-based dose accumulation (t = 3.82, 5.21, 4.58, 5.17, 2.05, P < 0.05). For EBRT combined with brachytherapy, the D_{2 cm³}, D_{1 cm³}, and D_{0.1 cm³} EQD2 doses to the rectal were 6.22, 7.61, 9.56 Gy higher than DIR-based doses, respectively, and the dosimetric differences were statistically significant (t = 9.40, 10.59, 7.87, P < 0.001). The joint prediction model yielded an area under the ROC curve of 0.788. The sensitivity and specificity of the optimal cut-off value were 0.850 and 0.660, respectively. Furthermore, the Hosmer-Lemeshow goodness-of-fit tests indicated high goodness-of-fit (P > 0.05). The prediction model for DIR-based dose accumulation of traditional predictors yielded areas under the ROC curves for D_{2 cm³} and D_{1 cm³} to the rectal of 0.784 and 0.763, respectively. The sensitivities of the optimal cut-off values were 0.850 and 0.750, respectively, and the specificities were 0.679 and 0.717, respectively. Conclusions There are dosimetric differences between the direct dose accumulation using EQD2 and DIR-based dose accumulation of 3D planning images for brachytherapy combined with EBRT. Both the joint prediction model and the DIR-based dose accumulation of D_{2 cm³} and D_{1 cm³} to the rectal are effective in predicting RLRI. Given the complex calculation of the joint prediction model, it is recommended that RLRI should be predicted through DIR-based dose accumulation of D_{2 cm³} and D_{1 cm³} to the rectal clinically.